Determine purity and quality of IROA labelled glucose
STUDY_TYPE
NMR and MS analysis
STUDY_SUMMARY
We demonstrate the global metabolic analysis ofCaenorhabditis elegansstress responses using a mass-spectrometry-based technique called isotopic ratio outlier analysis (IROA). In an IROA protocol, control and experimental samples are isotopically labeled with 95 and 5%13C, and the two sample populations are mixed together for uniform extraction, sample preparation, and LC-MS analysis.To illustrate the utility of IROA for global metabolomics, we exposed wild-type (N2) worms to a heat shock (30 min heat shock at 33 C), which causes significant, widespread changes in metabolism. We collected and analyzed material from the exometabolome (all material that worms release in the supernatant) and the endometabolome (homogenized total extracts from the worm bodies).
INSTITUTE
University of Florida
DEPARTMENT
Biochemistry & Molecular Biology
LAST_NAME
Stupp
FIRST_NAME
Gregory
EMAIL
stuppie@ufl.edu
STUDY_COMMENTS
Determine purity and quality of IROA labelled glucose
The goal of the study was to determine whether there is a set of metabolites that differentiate people who have knee OA and show radiographic disease progression over 18 months from those who have knee OA and do not show disease progression over the same time period.
This metabolomics pilot and feasibility (P & F) study was conducted to provide data to be used to gain a better understanding of metabolic alterations in people with knee osteoarthritis (OA) and to discover novel biomarkers of the disease. The goal of the metabolomics study was to determine if metabolic differences, detected by a comprehensive metabolomics analysis, can be used to distinguish people who will develop symptomatic knee OA from those who will not. For this metabolomics study, individuals participating in T1 or T1* with 5-year follow-up at T2 were selected. At T2 subjects were on average 68.1(9.12) years old with an average BMI of 31.4(7.01) with 32% men and one-third African American. All had weight-bearing posterior-anterior knee films obtained with the Synaflexer positioning device at both time points and read paired for Kellgren-Lawrence grade and minimum joint space. Urine samples (second morning void) collected from 36 overweight or obese participants in the JoCo at T1 or T1* were selected from two subgroups (a group that developed radiographic osteoarthritis (n=16) and an age, race, sex, and BMI matched group that did not develop osteoarthritis (n=20). Radiographic knee OA was defined as Kellgren-Lawrence grade 2-4 at T2 in a person with Kellgren-Lawrence grade 0 or 1 at T1 or T1*.
Metabolomics Involved in Early Life Antibiotic Exposures(DuraSTAT-Cecal)
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
In the DuraSTAT sub-study, a total of 18 samples from 8 week old, female C57BL/6 mice; comprised of 6 urine samples, 6 cecal content samples and 6 liver tissue samples were analyzed. Three mice/matrix were given STAT penicillin and 3 mice/matrix were non-treated Controls. The mice were housed with conventional bedding and fed a high fat diet.
Metabolomics Involved in Early Life Antibiotic Exposures(DuraSTAT-Liver)
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
In the DuraSTAT sub-study, a total of 18 samples from 8 week old, female C57BL/6 mice; comprised of 6 urine samples, 6 cecal content samples and 6 liver tissue samples were analyzed. Three mice/matrix were given STAT penicillin and 3 mice/matrix were non-treated Controls. The mice were housed with conventional bedding and fed a high fat diet.
Metabolomics Involved in Early Life Antibiotic Exposures(DuraSTAT-Urine)
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
In the DuraSTAT sub-study, a total of 18 samples from 8 week old, female C57BL/6 mice; comprised of 6 urine samples, 6 cecal content samples and 6 liver tissue samples were analyzed. Three mice/matrix were given STAT penicillin and 3 mice/matrix were non-treated Controls. The mice were housed with conventional bedding and fed a high fat diet.
Metabolomics Involved in Early Life Antibiotic Exposures(TranSTAT-Cecal)
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
In the TranSTAT sub-study, a total of 18 samples from 8 week old, female Swiss webster mice; comprised of 6 serum samples, 6 cecal content samples and 6 liver tissue samples were analyzed. Three mice/matrix were inoculated with cecal contents from STAT mice and 3 mice/matrix were inoculated with cecal contents from Control mice. The mice were housed with conventional bedding and fed a high fat diet.
Metabolomics Involved in Early Life Antibiotic Exposures(TranSTAT-Liver)
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
In the TranSTAT sub-study, a total of 18 samples from 8 week old, female Swiss webster mice; comprised of 6 serum samples, 6 cecal content samples and 6 liver tissue samples were analyzed. Three mice/matrix were inoculated with cecal contents from STAT mice and 3 mice/matrix were inoculated with cecal contents from Control mice. The mice were housed with conventional bedding and fed a high fat diet.
Metabolomics Involved in Early Life Antibiotic Exposures(TranSTAT-Serum)
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
In the TranSTAT sub-study, a total of 18 samples from 8 week old, female Swiss webster mice; comprised of 6 serum samples, 6 cecal content samples and 6 liver tissue samples were analyzed. Three mice/matrix were inoculated with cecal contents from STAT mice and 3 mice/matrix were inoculated with cecal contents from Control mice. The mice were housed with conventional bedding and fed a high fat diet.
Metabolomics Involved in Early Life Antibiotic Exposures(NOD-Cecal)
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
In the NOD sub-study, a total of 18 samples from 6 week old, male NOD/ShiLtj mice; comprised of 6 serum samples, 6 cecal content samples and 6 liver tissue samples were analyzed. Three mice/matrix were exposed to PAT and 3 mice/matrix were non-exposed Controls. The mice were housed with SPF (Helicobacter neg/MNV neg) bedding and fed a normal diet.
Metabolomics Involved in Early Life Antibiotic Exposures(NOD-Liver)
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
In the NOD sub-study, a total of 18 samples from 6 week old, male NOD/ShiLtj mice; comprised of 6 serum samples, 6 cecal content samples and 6 liver tissue samples were analyzed. Three mice/matrix were exposed to PAT and 3 mice/matrix were non-exposed Controls. The mice were housed with SPF (Helicobacter neg/MNV neg) bedding and fed a normal diet.
Metabolomics Involved in Early Life Antibiotic Exposures(NOD-Serum)
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
In the NOD sub-study, a total of 18 samples from 6 week old, male NOD/ShiLtj mice; comprised of 6 serum samples, 6 cecal content samples and 6 liver tissue samples were analyzed. Three mice/matrix were exposed to PAT and 3 mice/matrix were non-exposed Controls. The mice were housed with SPF (Helicobacter neg/MNV neg) bedding and fed a normal diet.
Metabolomics Involved in Early Life Antibiotic Exposures(EstroSTAT-Liver )
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
In the EstroSTAT sub-study, a total of 18 samples from 23 week old, female C57BL/6 mice; comprised of 6 urine samples, 6 serum samples and 6 liver tissue samples were analyzed. Three mice/matrix were given STAT penicillin and 3 mice/matrix were non-treated Controls. The mice were housed with conventional bedding and fed a Low phyto-estrogen diet.
Metabolomics Involved in Early Life Antibiotic Exposures(EstroSTAT-Serum)
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
In the EstroSTAT sub-study, a total of 18 samples from 23 week old, female C57BL/6 mice; comprised of 6 urine samples, 6 serum samples and 6 liver tissue samples were analyzed. Three mice/matrix were given STAT penicillin and 3 mice/matrix were non-treated Controls. The mice were housed with conventional bedding and fed a Low phyto-estrogen diet.
Metabolomics Involved in Early Life Antibiotic Exposures(EstroSTAT-Urine)
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
In the EstroSTAT sub-study, a total of 18 samples from 23 week old, female C57BL/6 mice; comprised of 6 urine samples, 6 serum samples and 6 liver tissue samples were analyzed. Three mice/matrix were given STAT penicillin and 3 mice/matrix were non-treated Controls. The mice were housed with conventional bedding and fed a Low phyto-estrogen diet.
Metabolomics Involved in Early Life Antibiotic Exposures(VGSTAT-Cecal)
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
In the VG STAT sub-study, a total of 18 samples from 7 week old, male C57BL/6 mice; comprised of 9 cecal content samples and 9 liver tissue samples were analyzed. Three mice/matrix were given penicillin VK, 3 were given penicillin G, and 3 mice/matrix were non-treated Controls. The mice were housed with conventional bedding and fed a normal diet.
Metabolomics Involved in Early Life Antibiotic Exposures(VGSTAT-Liver)
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
In the VG STAT sub-study, a total of 18 samples from 7 week old, male C57BL/6 mice; comprised of 9 cecal content samples and 9 liver tissue samples were analyzed. Three mice/matrix were given penicillin VK, 3 were given penicillin G, and 3 mice/matrix were non-treated Controls. The mice were housed with conventional bedding and fed a normal diet.
Human subjects were given high PUFA diet for 21 days then converted to high diet for another 21 days. Plasma samples were drawn during the feeding process 7 visits.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Plasma metabolomics: Comparison of non-diabetic controls with T1D patients
STUDY_TYPE
Drug effect study
STUDY_SUMMARY
Non-diabetic controls whose metabolites were compared to T1D patients with and insulin. Seven C-peptide?negative T1D subjects were studied on two occasions: during insulin treatment and the other following withdrawal of insulin for 8 h compared with matched healthy ND participants
Metabolomics Analysis of Thermally Challenged Mayfly Larvae (NMR analysis)
STUDY_TYPE
Metabolomic analysis of mayflies
STUDY_SUMMARY
The purpose of this study was to examine the metabolic profiles of mayfly (Centroptilum triangulifer) larvae subjected to thermal challenge. This species is unusual in terms of its ease of culture, and its suitability as a laboratory test organism. Our purpose here was to examine how an environmentally realistic thermal challenge affects the physiology of this organism. In this study, we obtained several types of insect species and we were able to show that NMR Metabolomics could be used to distinguish among the different types of larvae.
Brophy and Askenazi hypothesize that postnatal renal maturation results in specific identifiable patterns of urinary metabolites and that these profiles will be altered in the presence of AKI. Their long-term goal is to identify novel metabolomics urinary profiles that can provide real-time evidence of evolving neonatal renal injury thereby allowing earlier diagnosis and treatment.This study includes 40 pre-term infants age 2 days. Twenty infants were identified as not having AKI (11 females, mean gestational age=182.8 days, mean birth weight=834.0 grams) and 20 infants were identified as having AKI (13 females, mean gestational age=183.9 days, mean birth weight=815.8 grams). There are no statistical differences between the two groups based on gender, gestational age, and birth weight.
INSTITUTE
RTI International
DEPARTMENT
RTI RCMRC
LAST_NAME
Sumner
FIRST_NAME
Susan
ADDRESS
3040 East Cornwallis Road, Research Triangle Park, NC 27709, USA.
Fetal metabolomic signature of exposure to iAs during pregnancy
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
This metabolomics pilot study was aimed to identify a fetal metabolomic signature of exposure to iAs during pregnancy. Fetal cord blood serum was collected immediately after delivery from a saline cleaned umbilical cord using an anticoagulant-free vacutainer tube, after clot formation the tube was centrifuged at 1200 rpm and the serum was collected and stored at -70°C. A subset of 50 cord serum samples were selected from the larger BEAR cohort to represent a wide range of iAs exposure as determined by iAs in drinking water (DW-iAs). The exposure during pregnancy was confirmed using U-tAs. A total of 50 cord blood serum samples were used in the metabolomics analysis The samples included 25 newborns with lower maternal iAs exposure levels (DW < 25?g As/L, mean U-tAs=16 ?g/L) and 25 newborns with higher maternal iAs exposure levels (DW> 25?g As/L, mean U-tAs =107 ?g/L).
INSTITUTE
RTI International
DEPARTMENT
Systems and Translational Sciences (STS)
LABORATORY
RTI RCMRC
LAST_NAME
Sumner
FIRST_NAME
Susan
ADDRESS
3040 East Cornwallis Roadm Research Triangle Park, NC 27709, USA
Effect of kinase inhibitors on FLT3-ITD AML cell metabolomes
STUDY_TYPE
Metabolomics analysis on the effect of kinase inhibitors on FLT3-ITD AML cell to identify changes in cell signaling networks
STUDY_SUMMARY
FLT3-ITD AML cells (MR2) obtained from mice were treated with two MEK kinase (GSK and AZD) at 10 uM versus media only control. Conditioned media aliquots cellular fractions comprised of two aliquots (tecnical replicates) for LC-MS and one for Western blot analyses were collected at 0, 4, 24, and 48 hours. The was repeated three times. HPLC-MS data were acquired for 24 samples from one experiment.
Environmental impact on metabolomics and food allergy
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
This metabolomics pilot and feasibility (P&F) was conducted to determine if varying the levels of environmental LPS exposure and immunization with the vaccine adjuvant alum alters host metabolism. Additionally, the metabolomics will identify biomarkers that can predict allergic disease development and or disease severity after a peanut challenge in hypersensitive mice. Information gained from the proposed studies may allow for the identification of individuals who are at risk or not at risk for the development of allergic disease. Furthermore, completion of these studies may lead to identification of biological targets that may be used to develop novel therapies to treat or prevent allergic disease via future funding.
Metabolic Profiling of Visceral and Subcutaneous Adipose Tissue from Colorectal Patients: GC-TOF MS analyis of subcutaneous and visceral adipose tissue samples
STUDY_TYPE
biomarker study
STUDY_SUMMARY
This West Coast Metabolomics Center pilot and feasibility project was granted Johanna Lampe (Fred Hutchinson Cancer Research Center at Univ. of Washington, In the current investigation, unbiased profiling of the metabolome and lipidome adipose tissue samples (visceral(VAT) and subcutaenous (SAT)) and serum of 50 patients, including stages I-IV, from the Fred Hutchinson Cancer Center and the German Cancer Research Center (Heidelberg, Germany) was conducted. The and metabolome of adipose tissue (VAT/SAT) and serum were analyzed using UPLC-QTOFMS analysis and GC-TOFMS analyses, respectively. The primary of this project were to 1) compare the metabolome and lipidome SAT adipose tissue of n=50 Colorectal Cancer Cell (CRC) patients, 2) the associations between the lipidome and metabolome in adipose tissue and serum of n=50 CRC patients and 3) test the associations between the of VAT and serum with the tumor stage of CRC patients.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
1315 Genome and Biomedical Sciences Facility451 Health Sciences DriveDavis, CA
Biomarkers for Depression in Human Cerebrospinal Fluid in a Population Sample
STUDY_TYPE
biomarker study
STUDY_SUMMARY
This West Coast Metabolomics Center pilot and feasibility project was granted Roel Ophoff (UC Los Angeles ) and Steve Horwath (UC Los Angeles ) . Major disorder (MDD) is one of the most debilitating disorders in the United States a 12-month prevalence of 6.7% in the adult population. The disorder affects of Americans daily and is a major health concern with enormous economic cost society at large. Criteria for MDD diagnosis and treatment are based on various and symptoms not always fitting into strict diagnostic categories such as Despite various known risk factors (such as family history, age, and gender), markers supporting diagnosis or prediction of MDD are unavailable. We have cerebrospinal fluid (CSF) and peripheral blood of more than 600 subjects from general population. For each of the participants we also obtained biometric as well as behavioral trait measures. One of the measures is the Beck Inventory (BDI), a well-established questionnaire for measuring severity of Based on the BDI, roughly 5% of participants suffer from severe depressive while most of these subjects are not under treatment or receiving any for depression In the current investigation, untargeted analysis of primary was conducted on age and gender matched human cerebrospinal fluid (CSF) and from subjects suffering with MDD ( n=50) and control subjects (n=50). were diagnosed as having MDD based on the Beck Depression Inventory.The primary of this study were to 1) identify metabolites which discriminate between with and without depression symptoms in the CSF and plasma and 2) how changes between CSF and plasma.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
1315 Genome and Biomedical Sciences Facility451 Health Sciences DriveDavis, CA
Metabolomic profiling of influenza: a 2009 pandemic H1N1 influenza in lean and mice (via blood and tissue)
STUDY_TYPE
Metabolomics analysis on the effec of diet-related obesity on the immune to pH1N1 infection
STUDY_SUMMARY
Lung samples were obtained at 15 weeks from 56 mice that had received either a low fat diet, or a high fat diet and that were uninfected, 4 days or 8 days post-infection.
Effect of diet and age on ovarian metabolome (via tissue)
STUDY_TYPE
Metabolomics analysis on the ovarian metabolome
STUDY_SUMMARY
Ovarian samples from twenty-one adult, female Cynomolgus monkeys were studied, of which were fed the Western #907 diet, and 13 of which were fed the Prudent diet. HPLC-MS data were acquired for the 21 samples.
Effect of diet and age on ovarian metabolome (serum metabolome compared to
STUDY_TYPE
Metabolomics analysis on the serum metabolome for comparison against the metabolome
STUDY_SUMMARY
Serum samples from twenty-one adult, female Cynomolgus monkeys were studied, of which were fed the Western #907 diet, and 13 of which were fed the Prudent diet. HPLC-MS data were acquired for the 21 samples.
Genetic effects of high fat diet on mouse fecal metabolomics
STUDY_TYPE
Metabolomics analysis on the effect of genetics and diet on the metabolism of GI tract and obesity
STUDY_SUMMARY
This study includes 72 female mice with 4 mice from each of the 18 mice Two mice from each strain were fed a high fat diet and two mice were fed a fat diet. The 36 mice fed a normal fat diet will serve as the controls. All are age 27.6 weeks or older at the time of sacrifice. UPLC-MS data was for all 72 samples.
Metabolic Profiling of Visceral and Subcutaneous Adipose Tissue from Colorectal Patients: UHPLC-QTOF MS analyis of serum samples
STUDY_TYPE
biomarker study
STUDY_SUMMARY
This West Coast Metabolomics Center pilot and feasibility project was granted Johanna Lampe (Fred Hutchinson Cancer Research Center at Univ. of Washington, In the current investigation, unbiased profiling of the metabolome and lipidome adipose tissue samples (visceral(VAT) and subcutaenous (SAT)) and serum of 50 patients, including stages I-IV, from the Fred Hutchinson Cancer Center and the German Cancer Research Center (Heidelberg, Germany) was conducted. The and metabolome of adipose tissue (VAT/SAT) and serum were analyzed using UPLC-QTOFMS analysis and GC-TOFMS analyses, respectively. The primary of this project were to 1) compare the metabolome and lipidome SAT adipose tissue of n=50 Colorectal Cancer Cell (CRC) patients, 2) the associations between the lipidome and metabolome in adipose tissue and serum of n=50 CRC patients and 3) test the associations between the of VAT and serum with the tumor stage of CRC patients.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
1315 Genome and Biomedical Sciences Facility451 Health Sciences DriveDavis, CA
EMAIL
ofiehn@ucdavis.edu
PHONE
(530) 754-8258
NUM_GROUPS
1
TOTAL_SUBJECTS
59
STUDY_COMMENTS
Lipidomics profiles for studyThis is the serum part of the studyLabel-ID os for all parts of the study---
A study of changes in lipid metabolism of ovarian cancer cells co-cultured with GC-TOF MS analysis
STUDY_TYPE
timecourse study
STUDY_SUMMARY
This West Coast Metabolomics Center pilot and feasibility project was granted Ernst Lengyel (University of Chicago).The biology of ovarian cancer (OvCa) is distinct from that of most epithelial tumors, in that hematogenous metastases rare, and ovarian tumors remain confined to the peritoneal cavity. The omentum, large pad of fat tissue (20x13x3cm) covering the bowel, is the most common site OvCa metastasis. It consists primarily of adipocytes, which become the microenvironment for the OvCa cells. The underlying hypothesis for this is that, in the presence of adipocytes, the metabolism of OvCa cells is and shifts towards lipid utilization, which provides energy that facilitates growth and metastasis. Preliminary results suggest that primary human omental secrete cytokines which promote the metastasis of OvCa cells to the omentum and subsequent invasion. Once metastasis has occurred, OvCa cells induce lipolysis omental adipocytes, and use the energy derived from these lipids to study the metabolic changes in the tumor microenvironment we have established a organotypic culture of the human omentum using primary human cells established patient tissue. Metabolic studies will be performed on adipocytes and OvCa individually, on conditioned media and on adipocytes and OvCa cells co-cultured our 3D model, with the goal of arriving at a comprehensive analysis of primary and lipids in the tumor microenvironment.In the current investigation, analysis of primary metabolites and complex lipids were conducted on adipocytes OvCa cells individually, on conditioned media and on adipocytes and OvCa cells in our 3D model. Analysis of oxylipins was conducted on conditioned media. To better understanding of the dynamic regulation of metabolic pathways we will perform metabolic flux analysis using labeled cells (13C-glucose, in the 3D culture model.The primary objective of this study is to gain insight the dynamic interactions between OvCa cells and human adipocytes with the of elucidating targets of therapeutic intervention.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
1315 Genome and Biomedical Sciences Facility451 Health Sciences DriveDavis, CA
EMAIL
ofiehn@ucdavis.edu
PHONE
(530) 754-8258
NUM_GROUPS
2
TOTAL_SUBJECTS
14
STUDY_COMMENTS
Lipidomics profiles for studyFor the co-culture Human Adipocytes were grown in of SKOV3ip1 ovarian cancer cellsFor control samples the adipocytes were grown the absence of SKOV3ip1 ovarian cancer cells---Exp design 2 x 14Final result is by merging results from both files and applying dilution factor.Reason was high concentration in positive mode onlyRaw Data File (Positive Mode_TGs) Data File (Positive Mode_Non-TGs) (dilution2)
A statistical analysis of the effects of urease pre-treatment on the of the urinary metabolome by gas chromatographymass spectrometry
STUDY_TYPE
Analytical Comparison
STUDY_SUMMARY
Urease pre-treatment of urine has been utilized since the early 1960s to remove levels of urea from samples prior to further processing and analysis by gas spectrometry (GCMS). Aside from the obvious depletion or elimination of urea, effect, if any, of urease pre-treatment on the urinary metabolome has not been in detail. Here, we report the results of three separate but related that were designed to assess possible indirect effects of urease pre-treatment the urinary metabolome as measured by GCMS. In total, 235 GCMS analyses performed and over 106 identified and 200 unidentified metabolites were across the three experiments. The results showed that data from urease samples (1) had the same or lower coefficients of variance among reproducibly metabolites, (2) more accurately reflected quantitative differences and the ratios among different urine volumes, and (3) increased the number of identifications. Overall, we observed no negative consequences of urease In contrast, urease pre-treatment enhanced the ability to distinguish between and biological sample types compared to no treatment. Taken together, these show that urease pre-treatment of urine offers multiple beneficial effects that any artifacts that may be introduced to the data in urinary metabolomics
Dysfunctional lipid metabolism underlies the effect of perinatal DDT exposure the development of metabolic syndrome
STUDY_TYPE
Chemical dosage and feeding study
STUDY_SUMMARY
Targeted metabolomic analysis of bile acids was performed on 15 mouse liver collected from mice euthanized at 9 months following consumption of a high fat w/o perinatal DDT exposure. Funded by the National Institute of Health (R00 R03 DK082724, U24 DK092993, U24 DK097154, T32 ES007059, and P60 DK020541), the Diabetes Association, and USDA-ARS intramural Project 5306-51530-019-00D. were analyzed by UPLC-MS/MS using a Waters Acquity UPLC and detected on an API QTrap (AB Sciex, Framingham, MA, USA) by multiple reaction monitoring (MRM) negative mode electrospray ionization.
Measurements were performed on serum using 6 month old C57/B10 control (n=6) and mdx (n=8) mice. 1D proton and carbon spectra were collected on these samples
INSTITUTE
University of Florida
DEPARTMENT
Department of Biochemistry and Molecular Biology / SECIM
LABORATORY
Arthur Edison
LAST_NAME
Edison
FIRST_NAME
Arthur
ADDRESS
R3-226 Academic Research Building, Department of Biochemistry & Molecular Biology, PO Box 100245, Gainesville, FL 32610-0245
Two groups of mixtures with 5 replicates each were each made using 20 synthetic metabolites. Some metabolites were at equal concentrations in both groups, and 10 metabolites differed between groups with half higher in group A, and half higher in group B.
INSTITUTE
University of Florida
DEPARTMENT
Department of Biochemistry and Molecular Biology /SECIM
LABORATORY
Arthur Edison
LAST_NAME
Arthur
FIRST_NAME
Edison
ADDRESS
R3-226 Academic Research Building, Department of Biochemistry & Molecular Biology, PO Box 100245, Gainesville, FL 32610-0245
Cold adaptation shapes the robustness of metabolic networks in Drosophila melanogaster
STUDY_TYPE
Time course during cold exposure for four genetic lines of flies
STUDY_SUMMARY
Metabolites of cold hardy versus cold susceptible flies were compared using N less than R-based metabolomics. We used 8 replicates per line (2 hardy lines, two susceptible lines), and sampled each line at three time points (before, during and after cold), giving rise to 96 samples total.
Factors for Epigenetic Silencing of Lung Cancer Genes
STUDY_TYPE
Metabolomic analysis of Plasma
STUDY_SUMMARY
To test the hypothesis that the propensity for silencing of tumor suppressor genes in the respiratory epithelium of chronic smokers by promoter hypermethylation is influenced by sequence variations that modify the activity of genes and microRNAÕs that directly or indirectly influence de novo methylation and chromatin remodeling.
This experiment is investigating the metabolome of men, healthy women, and with Polycystic Ovary Syndrome (PCOS) with and without Obstructive Sleep Apnea
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Impact of insulin deprivation and treatment on sphingolipid distribution in muscle subcellular compartments of streptozotocin-diabetic C57Bl/6 mice
STUDY_TYPE
Insulin depravation
STUDY_SUMMARY
Experiments were conducted using 13-wk-old male C57BL/6J mice (Jackson Bar Harbor, ME). Mice were housed individually with free access to water and (TD.10112; Harlan Laboratories, Indianapolis, IN), with a 12:12-h light-dark and temperature and humidity control. Mice were acclimated for 1 wk prior to beginning of the experiment. The protocol was approved by the Mayo Clinic Animal Care and Use Committee. Following a 6-h fast, mice were given injections of STZ (125 mg/kg; in sodium acetate buffer, pH = 4.5) (67). were repeated on the following day. Control animals received intraperitoneal of vehicle. Only mice that displayed blood glucose ?300 mg/dl and an increase blood ketones (both values by Precision Xtra glucometer; Abbott Laboratories, Park, IL), hyperphagia, and polyuria and were positive for urine glucose via dipstick (Uristix, Bayer, Pittsburgh, PA) on day 7 after the first STZ dose included in the experiment. Animals that were positive for STZ diabetes LinBit subcutaneous insulin implant (LinShin Canada, Toronto, ON, Canada) (79) pentobarbital sodium anesthesia (Nebutal, 40 mg/kg of body wt) according to the protocol. Each animal received two subcutaneous implants (total dose: 0.2 U/24 for >30 days, 10 U/kg for 20-g mice). Insulin treatment was continued for 3 wk. animals (C; n = 13) received blank implants. Diabetic control was confirmed by measurements of blood and urinary glucose. In some cases, when urine glucose present and blood glucose was >288 mg/dl, the animal received a third implant. insulin treatment was continued until initially lower plasma glucose content in animals reached control values. Three weeks following implantation, diabetic were divided randomly into diabetic-treated (D + I; n = 13) and (D ? I; n = 13) groups. Insulin implants were removed from the D ? I group pentobarbital anesthesia, which led to the return of the diabetic phenotype 24 h. Animals from the D + I group continued on insulin treatment (Fig. 1). At age of 18 wk, animals from all groups were analyzed for body composition by an Body Composition Analyzer (EchoMRI, Houston, TX) and euthanized by decapitation wk after the initial STZ or vehicle dose. Figure 1 depicts the timeline of the and blood glucose profiles for each experimental group. Additional animals were for estimation of skeletal muscle insulin sensitivity by acute insulin The mice were divided into the C (n = 6), D ? I (n = 7), and D + I (n = 7) and followed appropriate experimental treatment, except for acute insulin 10 min prior to euthanization by pentobarbital overdose. Figure 1 of the PDF of the article summarizes the study design
Disruption of Zinc homeostasis can impair maternal glucocorticoid metabolism: on the developing fetus
STUDY_TYPE
steroid panel in pregnant rats
STUDY_SUMMARY
Steroids play a broad and vital role in regulation of gene expression, sexual characteristics, maturation, reproduction, and neurological functions; an imbalance in steroid metabolism is also linked to development and of many diseases including autism. Prenatal stress of different nature has been to affect both the mother and the offspring. Adverse nutritional conditions gestation can impair the maternal hypothalamic-pituitary-adrenal axis (HPA) and the fetus to high levels of glucocorticoids (GC). Evenwhen GC are required for brain development; an increased exposure of the fetus to GC as a consequence of stress can affect fetal hypothalamic-pituitary-gonad axis (HPG) development, neurogenesis, and have a long term impact on the offsprings mental health. zinc availability can occur during pregnancy as a consequence of different (nutritional deficiency, infections, diabetes, alcohol consumption, and to certain toxicants). Importantly, several of these gestational conditions been linked to autism. In fact, alterations in maternal zinc homeostasis upon to select environmental stressors (e.g. the phthalate plasticizer phthalate (DEHP)) that have become increasingly common since the industrial may underlie the recent rise in the incidence of autism.Alterations in maternal homeostasis could expose the fetus to high GC concentrations secondary to a maternal GC production and/or to a decreased capacity of the placenta to GC to inactive metabolites. The overall goal of this proposal is to investigate alterations in zinc homeostasis during gestation triggered by either a marginal nutrition or exposure to an environmental pollutant (the phthalate plasticizer phthalate (DEHP)) can impair maternal and fetal endocrine signaling leading to fetal brain development.
Impact of anesthesia and euthanasia on metabolomics of mammalian tissues: in a C57BL/6J mouse model
STUDY_TYPE
Anesthesia effect study
STUDY_SUMMARY
We examined the effect of several commonly-used methods of anesthesia and for collection of skeletal muscle, liver, heart, adipose and serum of C57BL/6J The data revealed tissue-specific impacts of different anesthesia and strategies. Based on these findings, we present a more optimal collection mammalian tissues and recommend that rodent tissues intended for metabolomics be collected under anesthesia rather than post-euthanasia.
INSTITUTE
University of Michigan
DEPARTMENT
Internal Medicine
LABORATORY
Evans Lab / Burant Lab
LAST_NAME
Charles
FIRST_NAME
Evans
ADDRESS
6321 Brehm Tower, 1000 Wall Street, Ann Arbor MI 48105
Monitoring In Vitro Response of Selenium-Treated Prostate Cells by 1H NMR Spectroscopy
STUDY_TYPE
Metabolite level response after treatment with organoselenium
STUDY_SUMMARY
Metabolomics analysis was performed on DU145 prostate cancer cells and PNT1A non-tumorigenic prostate cells after treatment with selenomethionine and Se-methylselenocysteine using 800 MHz Bruker NMR spectrometer on 18 cell samples.
Association of Metabolic Profile and Microbiome in Chronic Pressure Ulcer Wounds
STUDY_TYPE
Single end-point analysis of biopsies from chronic pressure ulcer wounds profiled for metabolomics and taxonomy
STUDY_SUMMARY
Chronic, non-healing wounds contribute significantly to the suffering of patients with co-morbidities in the clinical population with mild to severely compromised immune systems. Normal wound healing proceeds through a well-described process. However, in chronic wounds this process seems to become dysregulated at the transition between resolution of inflammation and re-epithelialization. Bioburden in the form of colonizing bacteria is a major contributor to the delayed headlining in chronic wounds such as pressure ulcers. However how the microbiome influences the wound metabolic landscape is unknown. Here, we have used a Systems Biology approach to determine the association between the taxonomic and metabolomic profile of wounds colonized by bacteria. Pressure ulcer biopsies were harvested from primary chronic wounds and bisected into top and bottom sections prior to analysis of microbiome by pyrosequencing and analysis of metabolome using 1H nuclear magnetic resonance (NMR) spectroscopy. Bacterial taxonomy revealed that wounds were colonized predominantly by three main phyla, but differed significantly at the genus level. While taxonomic profiles demonstrated significant variability between wounds, metabolic profiles shared significant similarity based on the depth of the wound biopsy. Association between taxonomy and metabolic landscape indicated significant wound-to-wound similarity in metabolite enrichment sets and metabolic pathway impacts, especially with regard to amino acid metabolism. To our knowledge, this is the first demonstration of a statistically robust correlation between bacterial colonization and metabolic landscape within the chronic wound environment.
INSTITUTE
Montana State University
DEPARTMENT
Chemistry and Biochemistry
LABORATORY
Ammons
LAST_NAME
Ammons
FIRST_NAME
Mary Cloud
ADDRESS
103 CBB, Montana State University, Bozeman, MT 59717
Labeling of cells was carried out in triplicate with each sample containing Cells were deprived of glucose or glutamine for 1 h then resuspended in 10mM D-glucose labeled or 4 mM [13C5]-U-glutamine labeled medium, respectively. At time cells were also activated with 5 ug/ml anti-CD3 and anti-CD28. Cells were (and activated) for 16 h when samples were spun down, and cells were in 200 ul ice cold methanol. All samples were immediately stored in -80°C.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
The human acute lymphoblastic leukemia cell line (Jurkat) was used to isolate a clones based on Noxa expression. JP6 is low Noxa, JP3 is high Noxa. Furthermore, a Noxa expressing plasmid was tranfected and stable clones were selected for a Noxa high model (N5). 10E6 cells were starved of glucose (A) or glutamine (B&C) for 3 hours and then fed 13C 1,2 glucose (A), 15N alpha nitrogen glutamine (B) or 15N amide nitrogen glutamine (C) for 24 hours. Cells were washed 1X in ice cold PBS and resuspended in -20C methanol. Quenched cells were snap frozen and stored at -80. For experiment A we would like to observe the contribution of labeled glucose into the synthesis of amino acids, specifically glycine and serine. For experiment B we are most interested in the nitrogen incorporation into aspartate. SCB edits: This fluxomics study requires measuring amino acids for M, M+1, M+2, and M+3 prioritizing glycine, serine, aspartate, asparagine, ornithine, citrulline, then as many as possible using a diamond hydride column and LCMS method (see CEvans).
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Sparing of muscle mass and function by passive loading in an experimental care unit model
STUDY_TYPE
time course + intervention
STUDY_SUMMARY
A unique experimental rat ICU model has been used allowing long-term (weeks) analyses of the effects of standardized unilateral passive mechanical loading skeletal muscle size and function and underlying mechanisms. Results show that mechanical loading alleviated the muscle wasting and the loss of associated with the ICU intervention, resulting in a doubling of the functional of the loaded versus the unloaded muscles after a 2-week ICU intervention.
Cardiac Resynchronization Therapy Induces Adaptive Metabolic Transitions in the Profile of Heart Failure
STUDY_TYPE
intervention
STUDY_SUMMARY
This prospective study consisted of 24 patients undergoing CRT for advanced HF 10 control patients who underwent catheter ablation for supraventricular but not CRT. Blood samples were collected before and 3 months after CRT. profiling of plasma samples was performed using gas chromatographymass and nuclear magnetic resonance.
THP-1 Human Monocyte cells (10^6) were seeded in RPMI 1640 with 0.5% FBS. The were incubated for 30 minutes in either no citrate, 1 mM citrate, or 6 mM Separately, cells were either incubated in 1 mM 13C6 citrate or 6mM 13C6 (Sigma-Aldrich #606081). After the 30 minute pre-incubation time, the cells harvested or stimulated with lipopolysaccharide (LPS) for 1 h or 30 min. Cells subsequently spun down and washed in 150mM ammonium acetate. Cell were respun the supernatant was discarded. Cells were flash frozen in liquid nitrogen and on dry ice.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Samples 4-34 are sera and feces from an experiment to determine the effects of on SCFA in Ang II-induced hypertension. Samples 35-59 are plasma samples fron experiment to determine the effects of ACE2 activator, DIZE on SCFA in pulmonary hypertension. Plasma samples were collected using heparin
STUDY_SUMMARY
Samples 4-34 are sera and feces from an experiment to determine the effects of on SCFA in Ang II-induced hypertension. Samples 35-59 are plasma samples fron experiment to determine the effects of ACE2 activator, DIZE on SCFA in pulmonary hypertension. Plasma samples were collected using heparin
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Liver and Plasma metaboites for 13C-glucose load in wild type, LIRKO and LIRFKO
STUDY_SUMMARY
Mice were fasted for 18 hr overnight then sacrificed or treated with (2 g/kg ip) and sacrificed 1 hr later by decapitation and liver was immediately and stored in liquid N2 and then at -80 C. Wild type (IR and IR/FoxO1 floxed) were sacrificed after fasting and 1 hr post-glucose treatment. Liver-specific receptor knockout (LIRKO) and insulin receptor/FoxO1 double knockout (LIRFKO) were sacrificed 1 hr post glucose treatment
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
THP-1 Human Monocyte cells (10^6) were seeded in RPMI 1640 with 0.5% FBS. The were incubated for 30 minutes in either no citrate, 1 mM citrate, or 6 mM Separately, cells were either incubated in 1 mM 13C6 citrate or 6mM 13C6 (Sigma-Aldrich #606081). After the 30 minute pre-incubation time, the cells harvested or stimulated with lipopolysaccharide (LPS) for 1 h or 30 min. Cells subsequently spun down and washed in 150mM ammonium acetate. Cell were respun the supernatant was discarded. Cells were flash frozen in liquid nitrogen and on dry ice.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Comparison of normal, lung adenocarcinoma and SCLC tissue metabolomes
STUDY_SUMMARY
In addition to the generation and analysis of metabolomics data on cell lines, of normal lung tissue, adenocarcinoma lung tissue and small cell lung carcinoma (seven samples/group) were processed and evaluated metabolite profile under the scope of the pilot and feasibility study. These data can be to the metabolite profiles defined in the SCLC and NSCLC cell lines and with the ABPP-determined metabolic kinases to identify distinct metabolic or biomarkers (?oncometabolites?) that distinguish small cell lung cancer from cell lung cancer.
1) Characterize plasma metabolome in Barth Syndrome 2) To implement targeted, quantitative studies on prospective biomarkers and metabolites of interest derived from the non-targeted phase.
Metabolomics Reveals that Aryl Hydrocarbon Receptor Activation by Environmental Chemicals Induces Systemic Metabolic Dysfunction in Mice (Part I)
STUDY_TYPE
drug dosage
STUDY_SUMMARY
12 mice were acclimatized for a week, taught to eat dough pills then half were treated with TCDF per pill per day for 5 days Also 10 AHR -/- mice were used and treated the same way
Untargeted metabolomic analysis of the small intestinal content of malnourished
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
A total of 8 samples from 6 week old, female C57BL/6 mice, treated for 3 weeks a malnourished diet or a control-fed isocaloric diet. Samples were taken from small intestinal fecal content at the terminus of the ileum.
INSTITUTE
University of Victoria
DEPARTMENT
The Uvic Proteomics and Metabolomics Innovation Centre
LAST_NAME
Borchers
FIRST_NAME
Christoph
ADDRESS
#3101-4464 Markham St Victoria, BC Canada, V8Z 7X8
Adult (14 weeks old) Sprague-Dawley rats showing at least three consecutive periods (4 day) of estrous cycles were randomly assigned to four groups: 1: 2: nicotine (6 mg/kg), 3: OC and 4: nicotine (6 mg/kg) + OC. Rats were exposed these treatments for a month. At the end of treatments, hippocampus was immediately frozen in liquid nitrogen. We are sending one side of hippocampi to Center for Integrated Metabolomics for analysis at the University of Florida.
Quick Comparison of Urine Metabolites in Human and SD Rats of Different Sex by UPLC-TOFMS and In-house Software Platform
STUDY_TYPE
Biomarker Discovery
STUDY_SUMMARY
Human urine samples were collected before breakfast from 14 male and 13 female post-graduate students, age from 23 to 29, on the morning of sample collection Male (n=8) and female (n=8) SD rats weighing between 220 and 250g were used. On morning of sample collection day, each rat was deprived of food and put in cage for 24h urine collection. All urine samples were frozen at -80°C prior to
Quick Comparison of Serum Metabolites in SD Rats of Different Sex by Untargeted and In-house Software Platform
STUDY_TYPE
Biomarker Discovery
STUDY_SUMMARY
Male (n=8) and female (n=8) SD rats weighing between 220 and 250g were used. On morning of sample collection day, each rat was deprived of food and put in cage for 24h urine collection. Then a blood sample (3-5ml) was collected from aorta of the rat under anesthesia and centrifuged to obtain serum. All urine serum samples were frozen at -80°C prior to analysis.
Sexual antagonism in exuded non-volatile metabolites in C. purpureus
STUDY_TYPE
male - female
STUDY_SUMMARY
The experimental approach seeks to test for sexual dimorphism in exuded metabolites in C. purpureus. The proposed research is creative and original in its inter-disciplinary approach and its use of a biochemically tractable to develop a much-needed link between natural selection for sexual dimorphism the molecular targets of that selection pressure.
Metabolomic-based investigation on the effects of antifungal agents in Candida
STUDY_TYPE
in vitro study/drug dosage
STUDY_SUMMARY
Our aim is to determine the metabolic effects of increasing doses of an agent on C. albicans metabolism (untargeted, steady state metabolomics). We culture in vitro Candida cells to the mid-logarithmic growth in liquid media at 37°C and then inoculate biological replicates (1ml) onto 22mm filters under vocuum filtration in sterile conditions. Subsequently, isolates be cultivated to midlogarithmic phase of growth on the same agar (RPMI-1640) to the antifungal agent has been added at a range of concentrations to achieve equivalent to 0 MIC (no drug), 0.0625 MIC, 0.125 MIC, 0.25 MIC, 0.5 MIC and 1.0 at 37°C. At mid-logarithmic phase of growth (12h) replicates will be quenched by immersion into a solvent mixture of 40% acetonitrile: 40% methanol: water precooled at -40°C. The resulting quenched isolate/solvent mixtrue will mechanically lysed by bead-beating with 0.1mm Zirconia beads in a tissue and then centrifuged to seperate out cell wall components. Supernatants will be and stored at -80°C until they will be sent to SECIM facility.
Determining the metabolic profile of wildtype and nos mutant Staphylococcus grown in media lacking glucose using targeted LC/MS
STUDY_TYPE
Single time point
STUDY_SUMMARY
Whole cells from wildtype, nos mutant, SrrAB mutant, SrrAB nos double mutant, complement strains will be isolated for targeted metabolite analysis. In supernatants (extracellular metabolites) will also be analyzed for their profile.
NIH WCMC Pilot & Feasibility Project: Metabolomics of Neonatal Pulmonary
STUDY_TYPE
Treatment and feeding study
STUDY_SUMMARY
Targeted metabolomic analyses of oxylipins were performed on 16 rat plasma and samples collected from rats euthanized at 14 days following exposure to growth and/or hyperoxia. Samples were analyzed by UPLC-MS/MS using a Waters Acquity and detected on an API 4000 QTrap (AB Sciex, Framingham, MA, USA) by multiple monitoring (MRM) after negative mode electrospray ionization.
The role of microbial metabolites in experimental liver disease
STUDY_TYPE
Targeted Metabolomic Analysis of plasma samples
STUDY_SUMMARY
Aim 1: Our experimental approach is to understand the effect of drinking water bacterial metabolite, Indole-3-propionic Acid (IPA), in liver disease in an alcohol model. Aim 2: Determine the levels of IPA in plasma of conventional in a chronic alcohol model.Aim 3: Determine the levels of IPA in plasma of WT (C57BL/6) and mutant SL (sublytic, which is a mouse with a point mutation in mice.
NIH WCMC Pilot & Feasibility Project: Metabolomics of Neonatal Pulmonary in human
STUDY_TYPE
Case-control study
STUDY_SUMMARY
Targeted metabolomic analyses of oxylipins were performed on 40 human umbilical plasma samples collected from infants born prematurely (gestational age <37 Samples were analyzed by UPLC-MS/MS using a Waters Acquity UPLC and detected on API 4000 QTrap (AB Sciex, Framingham, MA, USA) by multiple reaction monitoring after negative mode electrospray ionization.
NIH WCMC Pilot & Feasibility Project: Metabolite changes associated with loss
STUDY_TYPE
Feeding study
STUDY_SUMMARY
Targeted metabolomic analyses of oxylipins, endocannabinoids, and ceramides performed on 18 mouse liver, adipose, hypothalamus, plasma, and muscle samples from mice euthanized at 18 weeks following consumption of three diet regimens induced lean, obese, and weight loss phenotypes. Samples were analyzed by using a Waters Acquity UPLC and detected on an API 4000 QTrap (AB Sciex, MA, USA) by multiple reaction monitoring (MRM) after negative mode electrospray
Metabolic contribution of pSymA and pSymB megaplasmid/chromid for multipartite meliloti cultured in minimal M9 medium
STUDY_TYPE
megaplasmid deletion
STUDY_SUMMARY
To understand the contribution of pSymA and pSymB to the metabolism of S. the intracellular metabolome was analyzed at five time points (exponential and growth phases) across the growth curve of strains with or without pSymA and/or grown in a defined, minimal medium (M9).
INSTITUTE
McMaster University
DEPARTMENT
Department of Biology
LAST_NAME
Finan
FIRST_NAME
Turlough
ADDRESS
Department of Biology, McMaster University, Hamilton, Canada L8S4K1
We analyzed metabolites in the brains of wild type mice and DJ-1 knockout mice. DJ-1 knockout mouse is a model of an inherited form of Parkinson's disease.
INSTITUTE
National Institute on Aging
DEPARTMENT
Laboratory of Neurogenetics
LABORATORY
Cell Biology and Gene Expression Section
LAST_NAME
Hauser
FIRST_NAME
David
ADDRESS
35 Lincoln Drive, BLDG 35, Room 1A-1012, Bethesda, MD 20892
Activity-Based Metabolic Profiling of M. tuberculosis H37Rv Rv1016
STUDY_TYPE
timecourse
STUDY_SUMMARY
These experiments involve incubating various proteins of unknown function in M. tuberculosis genome with whole-cell lysate and assaying changes in levels over time (e.g. 0, 15, 30min) to try to infer what reaction they might
INSTITUTE
Weill Cornell Medical College
DEPARTMENT
Microbiology and Immunology
LAST_NAME
Rhee
FIRST_NAME
Kyu
ADDRESS
Department of Microbiology and Immunology, Weill Cornell Medical College, 1300 Avenue, New York, NY
EMAIL
kyr9001@med.cornell.edu
PHONE
-
NUM_GROUPS
3 replicates X 3 timepoints
STUDY_COMMENTS
The timepoints in the datafiles refer the amount of time (in minutes) that each was incubated with lysate.The units for 'mzmed' are mass/charge.The units for are seconds (retention time).The units for all the other data columns in the are arbitrary; they are integrated peak counts.In this study, Rv1713 was with lysate with and without 1mM GTP added as a co-factor.
Activity-Based Metabolic Profiling of M. tuberculosis H37Rv Rv3722c
STUDY_TYPE
timecourse
STUDY_SUMMARY
These experiments involve incubating various proteins of unknown function in M. tuberculosis genome with whole-cell lysate and assaying changes in levels over time (e.g. 0, 15, 30min) to try to infer what reaction they might
INSTITUTE
Weill Cornell Medical College
DEPARTMENT
Microbiology and Immunology
LAST_NAME
Rhee
FIRST_NAME
Kyu
ADDRESS
Department of Microbiology and Immunology, Weill Cornell Medical College, 1300 Avenue, New York, NY
EMAIL
kyr9001@med.cornell.edu
PHONE
-
STUDY_COMMENTS
The timepoints in the datafiles refer the amount of time (in minutes) that each was incubated with lysate.The units for 'mzmed' are mass/charge.The units for are seconds (retention time).The units for all the other data columns in the are arbitrary; they are integrated peak counts.In this study, Rv1713 was with lysate with and without 1mM GTP added as a co-factor.
Mice were fed with a TFD for 8 or 24 weeks to induce NAFLD or NASH, Targeted analyses examined diacylglycerols and ceramides in 6-8 mice per group 4 groups including 8 week control, 24 week control, 8 week TFD, and 24 week Samples were analyzed via UHPLC-HRMS
INSTITUTE
University of Florida
DEPARTMENT
Chemistry
LABORATORY
Yost Laboratory
LAST_NAME
Patterson
FIRST_NAME
Rainey
ADDRESS
214 Leigh Hall, University of Florida, Gainesville, FL 32611
Serum samples from Mla patients responsive or not responsive to chemotherapy
STUDY_SUMMARY
In the current study we will perform global metabolic profiling on serum obtained at diagnosis from pediatric AML patients (n=20) treated under St. Jude clinical trial to identify potential biomarkers of clinical significance. These include 10 responders and 10 non responders. In a subset of patients (n=7), we matched samples that were obtained at remission allowing us to determine the in serum metabolome at diagnosis and after remission followed by investigation the metabolome change analysis with clinical response.
Short-chain fatty acid analysis in bronchoalveolar lavage fluid (BAL SCFA)
STUDY_TYPE
We will correlate the bacterial gene abundance with the metabolite concentration
STUDY_SUMMARY
The study is intended to find if correlation exists between the abundance of bacterial gene for pyruvate ferredoxin oxidoreductase (PFOR) and short-chain fatty acids concentration in bronchoalveolar lavage fluid from patients with HIV-Associated Bacterial Pneumonia.
INSTITUTE
University of Michigan
DEPARTMENT
Pulmonary Medicine(New York University School of Medicine)
LABORATORY
Weiden Lab(New York University School of Medicine)
LAST_NAME
Weiden
FIRST_NAME
Michael
ADDRESS
New York
EMAIL
michael.weiden@nyumc.org
PHONE
212-263-6479
SUBMIT_DATE
2014-03-26
NUM_GROUPS
2
TOTAL_SUBJECTS
39
STUDY_COMMENTS
PFOR stands for pyruvate ferredoxin oxidoreductase gene
Lung contusion is a major risk factor for the development of acute respiratory syndrome. Hypoxia-inducible factor-1? is the primary transcription factor that responsible for regulating the cellular response to changes in oxygen tension. set to determine if hypoxia-inducible factor-1? plays a role in the of acute inflammatory response and injury in lung contusion.Nonlethal unilateral lung contusion was induced in a hypoxia reporter mouse model and 2 cell-specific hypoxia-inducible factor-1? conditional knockout mice. The mice killed at 5-, 24-, 48-, and 72-hour time points, and the extent of systemic and hypoxia was assessed. In addition, injury and inflammation were assessed by bronchoalveolar lavage cells (flow cytometry and cytospin), albumin injury), and cytokines (inflammation). Isolated type 2 cells from the factor-1? conditional knockout mice were isolated and evaluated for cytokines following lung contusion. Finally, the role of nuclear factor-?B and as intermediates in this interaction was studied.
INSTITUTE
University of Michigan
DEPARTMENT
Surgery
LABORATORY
Raghavendran Lab
LAST_NAME
Thomas
FIRST_NAME
Bivin
ADDRESS
Ann Arbor, MI
EMAIL
bthomas@umich.edu
PHONE
734-615-7142
NUM_GROUPS
4
TOTAL_SUBJECTS
8
STUDY_COMMENTS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245055/ : HIF1 (+/+) stands for reporter mouse modelHIF1 (-/-) stands for type 2 cell-specific factor-1? conditional knockout
Metabolic analysis of Parp1 ko/wt Saline & Bleo Mouse Lung Fiboblasts and Human & Normal Lung Fiboblasts (Part 2)
STUDY_TYPE
Glycolysis/TCA/Nucleotide analysis. Ceramide analysis for parp1 wild type lung after saline or bleomycin treatment.
STUDY_SUMMARY
This study is a part of series performed for the same researcher through grant program, so the publication is relevant reference for other studies ST000183)This specific experiment is a small pilot study to establish method it includes four biological replicas of identical cell cultures after the treatment and a single tissue sample.
Colorectal Cancer Detection Using Targeted Serum Metabolic Profiling
STUDY_SUMMARY
Colorectal cancer (CRC) is one of the most prevalent and deadly cancers in the Despite an expanding knowledge of its molecular pathogenesis during the past decades, robust biomarkers to enable screening, surveillance, and therapy of CRC are still lacking. In this study, we present a targeted liquid mass spectrometry-based metabolic profiling approach for identifying biomarker that could enable highly sensitive and specific CRC detection using human serum In this targeted approach, 158 metabolites from 25 metabolic pathways of significance were monitored in 234 serum samples from three groups of patients CRC patients, 76 polyp patients, and 92 healthy controls). Partial least analysis (PLS-DA) models were established, which proved to be powerful for CRC patients from both healthy controls and polyp patients. Receiver operating curves generated based on these PLS-DA models showed high sensitivities (0.96 0.89, respectively, for differentiating CRC patients from healthy controls or patients); good specificities (0.80 and 0.88), and excellent areas under the (0.93 and 0.95) were also obtained. Monte Carlo cross validation (MCCV) was applied, demonstrating the robust diagnostic power of this metabolic profiling
Despite the fact that colorectal cancer (CRC) is one of the most prevalent and deadly cancers in the world, the development of improved and robust biomarkers to enable screening, surveillance, and therapy monitoring of CRC continues to be evasive. In particular, patients with colon polyps are at higher risk of developing colon cancer; however, noninvasive methods to identify these patients suffer from poor performance. In consideration of the challenges involved in identifying metabolite biomarkers in individuals with high risk for colon cancer, we have investigated NMR-based metabolite profiling in combination with numerous demographic parameters to investigate the ability of serum metabolites to differentiate polyp/CRC patients from healthy subjects. We also investigated the effect of disease risk on different groups of biologically related metabolites. Our study may explain some of the challenges and promise a novel avenue for future metabolite profiling methodologies.
Vitamin B6 supplementation with 10 mg/d pyridoxine-HCl for 28-d was given to oral contraceptive (OC) users who initially had vitamin B6 deficiency (PLP < 30 nmol/L). Samples are analyzed before and after supplementation. In addition samples from OC users with low (PLP < 30 nmol/L) , middle (PLP 31-99 nmol/L) and high (PLP > 100 nmol/L) vitamin B6 concentration are compared.
Chronic mild stress and Lactobacillus experiments on mice
STUDY_SUMMARY
Mice were devided into three groups (Naive untreated, Stressed untreated, Stressed + Lacto). The stressed groups were subjected to unpredictable chronic mild stress for seven weeks. Three weeks into the protocol, the +Lacto groups were administered probiotic Lactobacillus daily.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Postprandial lipids are lower after vertical sleeve gastrectomy (VSG) surgery and this efect is independent of lipid absorption and chylomicron production. This poses a question of where the lipids are going. In order to test the hypothesis that intestinal oxidation of lipids is increased, Sham or VSG animals were gavaged with glycerol trioleate or water and sacrificed 2h later.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Conjugated linoleic acid (CLA) study in LDLR-/- mice
STUDY_TYPE
Acylcarnitine analysis
STUDY_SUMMARY
LDLR-/- mice were fed a high fat high sucrose diet with either 9,11 CLA or 10,12 CLA. Control groups included no supplementation or caloric restriction to mirror weight loss seen in CLA group. Mice were sacrificed and blood was collected into EDTA tubes. Isolated plasma was immediately frozen at -80C. Adipose tissue from gonadal fat (epididymal white adipose tissue, EWAT) and subcutaneous fat (inguinal white adipose tissue, IWAT) and liver were harvested, snap frozen in liquid nitrogen, and immediately frozen at -80C. An aliquot of thawed plasma was prepared for this project and frozen in an eppendorf tube. Small pieces of frozen tissue were cut and weighed on dry ice and packaged in individual foil packets for this project. **Note: tissue weight is approximate**
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Tumor neurospheres were grown in culture until ~90% confluent. Media was changed to contain 1mM acetate. After 24h, 0h time points were collected and media was changed on all other cells to 1mM 13C-acetate containing media. Cells were then collected at their various time points, 1, 3, 24, 48, or 72 hours. Cells were collected into 15mL tubes, spun down at 100xg for 1min and media aspirated. Pellet was washed (not resuspended) in 150mM ammonium acetate. This was then aspirated off and the cells snap frozen and stored at -80C until all time points complete to ship on dry ice. 0h, 1h, and 3h A, B, and C samples will have gTn by HILIC + TCA by GCMS done on them, while 0h, 1h, and 3h D, E, and F will have FAMES and DG & PC analysis done on them. 24h, 48h, and 72h A, B, and C samples will have FAMES analysis done on them.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Insulin-resistant subjects develop more severe and diffuse coronary artery atherosclerosis than insulin sensitive control but the mechanisms that mediate the atherosclerosis phenotype are unknown. The objective of this study is to investigate whether the severity of atherosclerosis is associated not only with lipoprotein concentrations, weight, blood pressure, biomarkers of inflammation and IR in an animal model but also changes in parameters that measure protein glycation. The experimental approach was to study normocholestrolemic pigs fed a high fat diet that also contained increased NaCl. The choice of pigs was driven by the fact that, like humans, they develop coronary artery and aortic atherosclerosis and insulin resistance. In addition, pigs have been used in many studies to define the mechanisms that mediate increased atherosclerosis in diabetes.
Metabolomics Approach to Identify Molecules and Pathways Involved in the Development of Atherosclerotic Coronary Artery Disease
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
Genetics play major roles in the development of atherosclerotic coronary artery disease (CAD). Despite tremendous efforts worldwide invested to decipher the genetic components controlling the development of CAD, the genetic architecture of CAD remains largely unclear. As part of an on-going effort to identify molecules and pathways involved in the development of atherosclerotic CAD, we propose to use rigorous angiographic criteria to define CAD phenotype for genomics and metabolomics study. We identified two extreme groups, namely “young CAD” group, who are very young individuals (age <= 40 years) proven to have severe CAD required revascularization, and “CAD-free elderly”, who are at very advanced age (Age >= 80 years) but have no angiographically apparent CAD. Phenotypically, these two groups are in sharp contrary. Conventional risk factors account for small portion of different phenotypes. We hypothesize that there are genetically programmed pathways and molecules accelerating atherosclerotic pathogenesis, in the “young CAD” patients and preventing the development of CAD in the “CAD-free elderly” patients. We sought to combine genomics and metabolomics approaches to profile and identify these pathways and molecules. Both plasma and urine samples from patients in these two groups, and their age matched control groups, will undergo unbiased metabolomics profiling with high throughput quantitative nuclear magnetic resonance (NMR) and mass spectrometry (MS) technology in RTI metabolomics core facility. Comprehensive statistic and multi-variant analytic approaches will be used to identify pathways and molecules significance to the pathogenesis of atherosclerosis. These data will be integrated with genomics data from next generation sequencing of genetic materials from the same groups of patients to further explore the molecular mechanisms underlying atherosclerosis and CAD.
IDH1R132H activity in glioma cell lines and tumnor tissue (2HG)
STUDY_TYPE
Regular
STUDY_SUMMARY
We developed genetically engineered mice to generate brain tumors with especific genetic lessions. The animals were split in three groups: NRAS, P53 knockdown, IDH1-R132H and ATRX knock down (NPAID); NRAS, P53 knockdown, IDH1-R132H (NPI); NRAS, P53 knockdown, (NshP53). From these tumor we obtain and culture tumor cells growth like neurospheres and attached cells.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
NSAID treatment alters the metabolomics profile of liver, kidney, lung, and heart in an experimental mouse model of heat stroke
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
The objective of this study is to exploit broad spectrum metabolomic analysis to identify new biomarkers of multi-organ damage that will improve heat stroke (HS) diagnosis and treatment. The central hypothesis is that HS will lead to significant alterations in multi-organ metabolomics profiles that will serve as markers of HS severity, which will be shifted and intensified further by the acute use of NSAIDs. To test this hypothesis, we will be performing broad spectrum metabolomics to identify alternations in the metabolic signatures of key organs (heart, liver, kidney, and lung) in a highly validated rodent HS model leveraging implantable radiotelemetry. We will then compare these results with already completed histological gene/protein expression analysis to determine the best metabolic markers of HS induced organ damage. The results from this study will aid in the identification of preventative measures to reduce HS risk, as well as in developing therapeutics to treat multi-organ damage and facilitate recovery. The proposed study will provide the first metabolic assessment of HS severity and NSAID use, which will support future studies in HS patients to validate novel biomarkers that will improve clinical assessment of organ damage and recovery.
Metabolomics and Childhood Obesity: A Pilot and Feasibility Study With Multiple Phenotypic Anchors
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
“Metabolomics” is a powerful new analytical approach for measuring and evaluating all small and intermediate sized metabolites in a variety of tissues or samples in conditions of health and disease. The purpose of this research is to determine if “metabolomics” can be used to address several important unanswered questions about obesity in children. First we will use metabolomics to identify patterns of metabolites in blood that are unique to obese children. We will then determine if these patterns are predictive of excessive weight gain and/or poor weight loss response in non-obese and obese children enrolled in an exercise program.
Experiment to test how different growth mediums affect bacterial growth. The supernatants of 17 strains of bacteria (10 grown in one medium and 7 grown in another medium) were submitted for metabolite analysis.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
Progesterone level effects on primary metabolites in uterus, blood, and ovaries (Part 2:Uterine flush)
STUDY_SUMMARY
In this experiment a hormonal protocol was applied to control follicle growth to yield larger or smaller preovulatory follicle and CLs and consequently different circulating Progesterone (P4) concentrations during early diestrus. The two different animal's group are: high or low progesterone levels. The effects of these progesterone levels was tested in the uterus of the cow.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
Metabolomic effects of metformin on mouse liver, intestine, and serum
STUDY_SUMMARY
Experiment to test the different metabolomic effects of two different doses of metformin (50mg vs 150 mg). A saline treatment group was used as a control. The effects were measured at the liver, intestine, and serum of the mouse.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
Role of medium in bacterial growth (HILIC chromatography)
STUDY_SUMMARY
Experiment to test how different growth mediums affect bacterial growth. The supernatants of 17 strains of bacteria (10 grown in one medium and 7 grown in another medium) were submitted for metabolite analysis.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
This experiment aimed to see the effects of Giardia Intestinalis on the small intestine of mice. The metabolites of the proximal and distal ends of the small intestine of healthy mice were compared to those of mice who had been infected with Giardia intestinalis for 7 days.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
Metabolomics of bovine uterine fluid at the onset of conceptus elongation
STUDY_TYPE
Prospective cohort study
STUDY_SUMMARY
The objective is to investigate changes in metabolomics of uterine lumen content of lactating dairy cows associated with the onset of conceptus (embryo and associated membranes) elongation. Lactating dairy cows had estrous cycles synchronized and were subjected to induced ovulation and timed artificial insemination (AI). The day of AI was considered study d 0. On d 15, uteri were flushed by transcervical catheterization and infusion of 20 mL of phosphate buffered solution with 0.1% of polyvinyl acetate. Recovered conceptuses were classified based on morphology/length as ovoid (OV; 1-4 mm), tubular (TUB; 5-19 mm) and filamentous (FIL; 20-85 mm). The first 20 mL infused in the uterus were recovered, placed in conical tubes and centrifuged at 2,000 × g at 4ᵒC. The supernatant was collect, aliquoted and stored at -80ᵒC for later analyses of fluid composition, including measurement of IFN-τ concentration. Cows with no conceptus recovered and no detection of IFN-τ in uterine flushing were considered as nonpregnant (NPREG). The experimental design was then considered a prospective cohort study with 4 independent groups (NPREG, OV, TUB, and FIL). The additional 5th group represents a specific physiological condition of cows within the study and it will be compared to TUB and FIL groups combined, working as a pilot study for future research.
INSTITUTE
University of Florida
DEPARTMENT
SECIM
LABORATORY
Laboratory of Reproduction and Nutrition of Dairy Cows
Metabolomics Approach to Allograft Assessment in Liver Transplantation
STUDY_TYPE
Retrospective analysis of biobanked liver tissue from organ donors
STUDY_SUMMARY
This pilot study is designed to apply several types of metabolomic analysis for liver allograft assessment with the aim of identifying candidate biomarkers for allograft function and to develop a methodology that could be applied to larger scale studies. The three main categories of metabolomic analysis are reflected in each of the specific aims, including a targeted profiling of central carbon metabolism, open lipidomic and metabolomic profiling for hypothesis generation and MALDI-IMS for tissue-based spatial analysis. Each of these approaches offers potential benefits that could be optimized in a protocol for larger scale studies depending the results of the pilot investigations.
INSTITUTE
Ochsner Multi-Organ Transplant Institute
DEPARTMENT
SECIM
LABORATORY
Abdominal Organ Transplantation
LAST_NAME
Seal
FIRST_NAME
John
ADDRESS
1514 Jefferson Highway, New Orleans, LA 70121
EMAIL
John.Seal@ochsner.org
PHONE
504-232-4253
NUM_GROUPS
3
TOTAL_SUBJECTS
Targeted analysis and open profiling: Control group - standard criteria donor (N=15); Experimental group - donation-after-cardiac-death donors (N=10). MALDI-IMS - standard criteria donor (N=10)
Unbiased profiling uncovers a crucial role for gut microbiome derived metabolites in modulating GI epithelial cell damage and mitigating GVHD.
STUDY_SUMMARY
Taxonomic alterations in the intestinal microbiota are being progressively associated with many diseases, including graft-versus host disease (GVHD). However, the impact of these alterations on microbial metabolites and by-products and their subsequent impact on disease processes, such as GVHD, are not known. Here we utilized a targetedn unbiased and blinded approach in a blinded fashion to identify novel alterations in the levels of microbial metabolites, specifically levels including the short chain fatty acid (SCFA) and endogenous histone deacetylase inhibitor (HDACi), butyrate, after allo-BMT. Surprisingly, alterations were observed only in intestinal epithelial cells (IECs) but not in the luminal contents. The reduced butyrate in IECs (CD326+) after allo-BMT resulted in decreased histone acetylation, which was restored upon local administration of exogenous butyrate. This resulted in improved IEC junctional integrity, increased anti-apoptotic proteins, decreased GVHD, and improved survival. Furthermore, alteration of endogenous microflora with 17 rationally selected strains of high butyrate producing Clostridia, also decreased GVHD and increased survival following allo-BMT in experiments performed at two different institutions. These data demonstrate an heretofore unrecognized role of microbial metabolites and suggests that local and specific alteration of microbial metabolites has direct salutary effects on GVHD target tissues and mitigates its severity.
Metabolites detected from human bronchoalveolar lavage
STUDY_SUMMARY
This is a preliminary trial to determine how viable this system will be to use on a much larger number of samples (up to 150). We would like to determine the range, number of metabolite species, and relative concentrations than can be detected in human bronchoalveolar lavage. We would also like to determine how clear the distinction is between the 3 patient groups as this will inform us as to how many of the 150 samples we need to run in the study proper.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
Metabolomic analysis on samples from rats expressing human amylin (cardiac tissue).
STUDY_SUMMARY
Human amylin proteotoxicity impairs protein biosynthesis, and alters major cellular signaling pathways in the heart, brain and liver of humanized diabetic rat model in vivo. The 37 amino acid hormone Amylin is cosecreted with insulin from ß cells in the pancreas. In prediabetic and obese humans, chronic amylin hypersecretion parallels the course of disease and is involved in the pathophysiology of beta cell destruction in the pancreas. Recent studies in rats with transgenic expression of beta cell amylin (HIP), we have discovered that human amylin is prone to misfolding and has proteotoxic effects in vivo, resulting in the induction of cell death paralleling the pathophysiology of neurodegenerative disease. These misfolded proteotoxic amylin proteins are found to migrate to both the brain and heart to induce both neurologic deficits and cardiac dysfunction. In the present study, we use nontargeted GCMS metabolomics analysis to investigate the metabolic consequences of amyloidogenic and cytotoxic amylin oligomers and diabetes in HIP heart, brain, liver, and plasma compared to wild type controls at 1 year of age. We identified that HIP hearts had 45 significantly altered metabolites by ttest (p<0.05) compared to wildtype control hearts (0.134.3 fold different,N=8/group). Similarly, we identified 30 metabolites significantly different in the HIP brain by ttest (p<0.05) compared to wildtype control brains (0.225.2 fold different (N=~10/group). HIP livers had 58 metabolites significantly altered by ttest (p<0.05) compared to wildtype livers (0.0199.4 fold different,N=~10/group. Pathway enrichment analysis identified a systemic alteration in protein biosynthesis in the heart and brain of HIP rats compared to wild type controls. Alterations in phenylalanine metabolism and aminoacyltRNA biosynthesis were specifically affected in heart and plasma. Tyrosine metabolism is affected across organs, including decreased tyrosine (heart), phenylalanine (heart, liver, brain), and increased fumarate (heart, liver, brain). Increased urea and urea cycle were identified in heart and liver. As protein degradation is a major upregulator of the urea cycle in human rat diabetic models, these findings suggest a broader connection between amylin, diabetes, protein catabolism, and effects on the urea cycle, which may contribute to the increased morbidity and mortality in diabetics at a multisystem level beyond the effects on glucose metabolism.
INSTITUTE
University of North Carolina
DEPARTMENT
McAllister heart Institute, Department of Internal medicine
LABORATORY
Multiple Centers
LAST_NAME
Ilaiwy
FIRST_NAME
Amro
ADDRESS
111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA
Metabolomic analysis on samples from rats expressing human amylin (brain tissue).
STUDY_TYPE
Non targeted metabolomics-Brain tissue
STUDY_SUMMARY
Human amylin proteotoxicity impairs protein biosynthesis, and alters major cellular signaling pathways in the heart, brain and liver of humanized diabetic rat model in vivo. The 37 amino acid hormone Amylin is cosecreted with insulin from ß cells in the pancreas. In prediabetic and obese humans, chronic amylin hypersecretion parallels the course of disease and is involved in the pathophysiology of beta cell destruction in the pancreas. Recent studies in rats with transgenic expression of beta cell amylin (HIP), we have discovered that human amylin is prone to misfolding and has proteotoxic effects in vivo, resulting in the induction of cell death paralleling the pathophysiology of neurodegenerative disease. These misfolded proteotoxic amylin proteins are found to migrate to both the brain and heart to induce both neurologic deficits and cardiac dysfunction. In the present study, we use nontargeted GCMS metabolomics analysis to investigate the metabolic consequences of amyloidogenic and cytotoxic amylin oligomers and diabetes in HIP heart, brain, liver, and plasma compared to wild type controls at 1 year of age. We identified that HIP hearts had 45 significantly altered metabolites by ttest (p<0.05) compared to wildtype control hearts (0.134.3 fold different,N=8/group). Similarly, we identified 30 metabolites significantly different in the HIP brain by ttest (p<0.05) compared to wildtype control brains (0.225.2 fold different (N=~10/group). HIP livers had 58 metabolites significantly altered by ttest (p<0.05) compared to wildtype livers (0.0199.4 fold different,N=~10/group. Pathway enrichment analysis identified a systemic alteration in protein biosynthesis in the heart and brain of HIP rats compared to wild type controls. Alterations in phenylalanine metabolism and aminoacyltRNA biosynthesis were specifically affected in heart and plasma. Tyrosine metabolism is affected across organs, including decreased tyrosine (heart), phenylalanine (heart, liver, brain), and increased fumarate (heart, liver, brain). Increased urea and urea cycle were identified in heart and liver. As protein degradation is a major upregulator of the urea cycle in human rat diabetic models, these findings suggest a broader connection between amylin, diabetes, protein catabolism, and effects on the urea cycle, which may contribute to the increased morbidity and mortality in diabetics at a multisystem level beyond the effects on glucose metabolism.
INSTITUTE
Duke University
DEPARTMENT
Sarah W. Stedman Nutrition and Metabolism Center
LABORATORY
Metabolomics lab
LAST_NAME
Ilaiwy
FIRST_NAME
Amro
ADDRESS
111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA
EMAIL
amroilaiwy@gmail.com, monte_willis@med.unc.edu
PHONE
210-596-0171
STUDY_COMMENTS
Brain tissue-Metabolomic analysis was performed at Duke Metabolomics lab
Metabolomic analysis on samples from rats expressing human amylin (hepatic tissue).
STUDY_SUMMARY
Human amylin proteotoxicity impairs protein biosynthesis, and alters major cellular signaling pathways in the heart, brain and liver of humanized diabetic rat model in vivo. The 37 amino acid hormone Amylin is cosecreted with insulin from ß cells in the pancreas. In prediabetic and obese humans, chronic amylin hypersecretion parallels the course of disease and is involved in the pathophysiology of beta cell destruction in the pancreas. Recent studies in rats with transgenic expression of beta cell amylin (HIP), we have discovered that human amylin is prone to misfolding and has proteotoxic effects in vivo, resulting in the induction of cell death paralleling the pathophysiology of neurodegenerative disease. These misfolded proteotoxic amylin proteins are found to migrate to both the brain and heart to induce both neurologic deficits and cardiac dysfunction. In the present study, we use nontargeted GCMS metabolomics analysis to investigate the metabolic consequences of amyloidogenic and cytotoxic amylin oligomers and diabetes in HIP heart, brain, liver, and plasma compared to wild type controls at 1 year of age. We identified that HIP hearts had 45 significantly altered metabolites by ttest (p<0.05) compared to wildtype control hearts (0.134.3 fold different,N=8/group). Similarly, we identified 30 metabolites significantly different in the HIP brain by ttest (p<0.05) compared to wildtype control brains (0.225.2 fold different (N=~10/group). HIP livers had 58 metabolites significantly altered by ttest (p<0.05) compared to wildtype livers (0.0199.4 fold different,N=~10/group. Pathway enrichment analysis identified a systemic alteration in protein biosynthesis in the heart and brain of HIP rats compared to wild type controls. Alterations in phenylalanine metabolism and aminoacyltRNA biosynthesis were specifically affected in heart and plasma. Tyrosine metabolism is affected across organs, including decreased tyrosine (heart), phenylalanine (heart, liver, brain), and increased fumarate (heart, liver, brain). Increased urea and urea cycle were identified in heart and liver. As protein degradation is a major upregulator of the urea cycle in human rat diabetic models, these findings suggest a broader connection between amylin, diabetes, protein catabolism, and effects on the urea cycle, which may contribute to the increased morbidity and mortality in diabetics at a multisystem level beyond the effects on glucose metabolism.
INSTITUTE
University of North Carolina
LABORATORY
Multiple Centers
LAST_NAME
Ilaiwy
FIRST_NAME
Amro
ADDRESS
111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA
Metabolomic analysis on samples from rats expressing human amylin (plasma).
STUDY_SUMMARY
Human amylin proteotoxicity impairs protein biosynthesis, and alters major cellular signaling pathways in the heart, brain and liver of humanized diabetic rat model in vivo. The 37 amino acid hormone Amylin is cosecreted with insulin from ß cells in the pancreas. In prediabetic and obese humans, chronic amylin hypersecretion parallels the course of disease and is involved in the pathophysiology of beta cell destruction in the pancreas. Recent studies in rats with transgenic expression of beta cell amylin (HIP), we have discovered that human amylin is prone to misfolding and has proteotoxic effects in vivo, resulting in the induction of cell death paralleling the pathophysiology of neurodegenerative disease. These misfolded proteotoxic amylin proteins are found to migrate to both the brain and heart to induce both neurologic deficits and cardiac dysfunction. In the present study, we use nontargeted GCMS metabolomics analysis to investigate the metabolic consequences of amyloidogenic and cytotoxic amylin oligomers and diabetes in HIP heart, brain, liver, and plasma compared to wild type controls at 1 year of age. We identified that HIP hearts had 45 significantly altered metabolites by ttest (p<0.05) compared to wildtype control hearts (0.134.3 fold different,N=8/group). Similarly, we identified 30 metabolites significantly different in the HIP brain by ttest (p<0.05) compared to wildtype control brains (0.225.2 fold different (N=~10/group). HIP livers had 58 metabolites significantly altered by ttest (p<0.05) compared to wildtype livers (0.0199.4 fold different,N=~10/group. Pathway enrichment analysis identified a systemic alteration in protein biosynthesis in the heart and brain of HIP rats compared to wild type controls. Alterations in phenylalanine metabolism and aminoacyltRNA biosynthesis were specifically affected in heart and plasma. Tyrosine metabolism is affected across organs, including decreased tyrosine (heart), phenylalanine (heart, liver, brain), and increased fumarate (heart, liver, brain). Increased urea and urea cycle were identified in heart and liver. As protein degradation is a major upregulator of the urea cycle in human rat diabetic models, these findings suggest a broader connection between amylin, diabetes, protein catabolism, and effects on the urea cycle, which may contribute to the increased morbidity and mortality in diabetics at a multisystem level beyond the effects on glucose metabolism.
INSTITUTE
University of North Carolina
LABORATORY
Multiple Centers
LAST_NAME
Ilaiwy
FIRST_NAME
Amro
ADDRESS
111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA
Determining the metabolic profile of wildtype, lrgAB, and atlA mutant Steptococcus mutans grown aerobically and anaerobically
STUDY_TYPE
Single time point, aerobic vs. anaerobic cultures
STUDY_SUMMARY
Whole cells from both aerobic and anaerobic cultures of wild-type,lrgAB and atlA strain will be isolated for analysis of the whole cytosolic metabolome. Supernatants will be also analyzed for their metabolite profile in wild type and lrgAB cultures.
INSTITUTE
University of Florida
DEPARTMENT
SECIM
LAST_NAME
Ahn
FIRST_NAME
Sang-Joon
ADDRESS
1395 Center Drive, Room D5-29 Gainesville FL 32610
The Development of Metabolomic Markers in African Bermudagrass (C. transvaalensis) for Sting Nematode (Belonolaimus longicaudatus) Response
STUDY_TYPE
Disease response in terms of nematode reproduction and root weight
STUDY_SUMMARY
The objective of the proposed pilot study is to identify metabolites up- and down-regulated in African bermudagrass that are tolerant and sensitive to the sting nematode and develop metabolomic markers for the highest expressed metabolites associated with tolerance. Future work will include additional accessions and species of bermudagrass, and testing under field conditions. Bermudagrass accessions identified as tolerant or sensitive by Pang et al. (2011) will be assessed under controlled greenhouse conditions to identify metabolites linked to sting nematode tolerance. Nematode response will be quantified through determination of root length and weight and the number of nematodes present 136 days after inoculation. Higher root length and weight indicate tolerance or resistance. Higher nematode counts indicate greater reproduction (i.e. a susceptible plant), while lower counts indicate that the accession may have some resistance. Metabolites from root tissue of these accessions will be compared to identify those associated with tolerance/resistance, and those that are associated with nematode infestation by comparing inoculated plants to uninoculated controls. Metabolomic markers will then be developed for the metabolites associated with tolerance/resistance. These markers will be used to guide future screening of bermudagrass accessions for breeding nematode-tolerant or -resistant varieties.
Metabolite comparison of mouse gastric tissue and glands
STUDY_SUMMARY
The goal of this project was to compare the metabolite profiles of the: mouse gastric antrum and the mouse gastric corpus, the mouse gastric antrum and the mouse gastric antrum isolated glands, and the mouse gastric corpus and the mouse gastric corpus isolated glands.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
Characterization and Plasticity of the Metabolome in Peripheral Cells in Bipolar I Disorder
STUDY_TYPE
Broad Spectrum LCMS
STUDY_SUMMARY
Patients with Bipolar I Disorder (BPI) and matched non-affected controls were recruited. Males and females from all races and ethnicities between the ages of 19-65 participated in the research. Skin biopsies were obtained and fibroblasts were isolated from each of these biopsies. A total of 1 x 〖10〗^7 fibroblasts cells were used for metabolomics. Cell pellets were flash frozen in liquid nitrogen and shipped on dry ice to the NIH Eastern Regional Comprehensive Metabolomic Resource Core at RTI International in North Carolina. Metabolomics will be determined using a broad spectrum metabolomics protocol by RTI
Metabolomics analysis of colon adenoma in African Americans
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
This NMR Metabolomics analysis was performed on feces samples derived from healthy (n = 10) and adenoma (n = 10) African American subjects with the goal of identifying perturbations in metabolomics profiles in colon cancer.
Distinctly perturbed metabolic networks underlie differential tumor tissue damages induced by immune modulator b-glucan in a two-case ex vivo non-small cell lung cancer study
STUDY_TYPE
tracer
STUDY_SUMMARY
[U-13C]-Glu SIRM study of ex vivo tissue slices in matched-pair tumor/non-tumor ex vivo tissue slices from two human patients with and withou beta-glucan.
INSTITUTE
University of Kentucky
DEPARTMENT
CESB
LAST_NAME
Fan
FIRST_NAME
Teresa
ADDRESS
Rm 516 Biopharm Complex, 789 S. Limestone St.,Univ. of Kentucky, Lexington, KY 40536
Investigation of metabolomic blood biomarkers for detection of adenocarcinoma lung cancer
STUDY_TYPE
Lung cancer case control biomarker discovery
STUDY_SUMMARY
Recently, the National Lung Cancer Screen Trial (NLST) demonstrated that low-dose CT (LDCT) screening could reduce mortality due to lung cancer by 20%. However, LDCT screening is largely hindered by high false-positive rates (96%), particularly in high-risk populations (heavy smokers), due to the low prevalence rates (less than 2%) of malignant tumors and high incidence of benign lung nodules. Consequently, complementary biomarkers that can be used in conjunction with LDCT screening to improve diagnostic capacities and reduce false-positive rates are highly desirable. Preferably, such complementary tools should be noninvasive and exhibit high sensitivity and specificity. The application of “-omic” sciences (genomics, transcriptomics, proteomics, and metabolomics) represents valuable tools for the discovery and validation of potential biomarkers that can be used for detection of NSCLC. Of these omic sciences, metabolomics has received considerable attention for its application in cancer. Metabolomics is the assessment of small molecules and biochemical intermediates (metabolites) using analytic instrumentation. Metabolites in blood are the product of all cellular processes, which are highly responsive to conditions of disease and environment, and represent the final output products of all organs forming a detailed systemic representation of an individual's current physiologic state. In this study, we used an untargeted metabolomics approach using gas chromatography time-of-flight mass spectrometry (GCTOFMS) to analyze the metabolome of serum and plasma samples both collected from the same patients that were organized into two independent case–control studies (ADC1 and ADC2). In both studies, only NSCLC adenocarcinoma was investigated. The overall objectives were to (i) determine whether individual or combinations of metabolites could be used as a diagnostic test to distinguish NSCLC adenocarcinoma from controls and (ii) to determine which, plasma or serum, provides more accurate classifiers for the detection of lung cancer. We developed individual and multimetabolite classifiers using a training test from the ADC1 study and evaluated the performance of the constructed classifiers, individually or in combination, in an independent test/validation study (ADC2). This study shows the potential of metabolite-based diagnostic tests for detection of lung adenocarcinoma. Further validation in a larger pool of samples is warranted.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
EMAIL
ofiehn@ucdavis.edu
PHONE
(530) 754-8258
STUDY_COMMENTS
SS = Sigma sample and is used as a quality control The first set (ADC1) used for biomarker development consisted of serum and plasma samples obtained from 52 stages I–IV NSCLC adenocarcinoma patients (52 plasma and 49 serum), and 31 healthy controls (31 pairs of serum and plasma) for a total of 163 samples. This set was regarded as the training set for biomarker discovery and classifier development. A second, independent case–control study (ADC2) consisting of serum and plasma samples collected from 43 stage I–IV NSCLC adenocarcinoma patients and 43 healthy controls (total 172 samples) was used as an independent test set for biomarker evaluation. A limitation of this study is the relatively small sample size for each cohort (52 cases, 31 controls for ADC1, and 43 cases and 43 controls for ADC2) because patient variability can be a big factor in smaller studies.
Investigation of metabolomic blood biomarkers for detection of adenocarcinoma lung cancer (part II)
STUDY_TYPE
Lung cancer case control biomarker discovery
STUDY_SUMMARY
Recently, the National Lung Cancer Screen Trial (NLST) demonstrated that low-dose CT (LDCT) screening could reduce mortality due to lung cancer by 20%. However, LDCT screening is largely hindered by high false-positive rates (96%), particularly in high-risk populations (heavy smokers), due to the low prevalence rates (less than 2%) of malignant tumors and high incidence of benign lung nodules. Consequently, complementary biomarkers that can be used in conjunction with LDCT screening to improve diagnostic capacities and reduce false-positive rates are highly desirable. Preferably, such complementary tools should be noninvasive and exhibit high sensitivity and specificity. The application of “-omic” sciences (genomics, transcriptomics, proteomics, and metabolomics) represents valuable tools for the discovery and validation of potential biomarkers that can be used for detection of NSCLC. Of these omic sciences, metabolomics has received considerable attention for its application in cancer. Metabolomics is the assessment of small molecules and biochemical intermediates (metabolites) using analytic instrumentation. Metabolites in blood are the product of all cellular processes, which are highly responsive to conditions of disease and environment, and represent the final output products of all organs forming a detailed systemic representation of an individual's current physiologic state. In this study, we used an untargeted metabolomics approach using gas chromatography time-of-flight mass spectrometry (GCTOFMS) to analyze the metabolome of serum and plasma samples both collected from the same patients that were organized into two independent case–control studies (ADC1 and ADC2). In both studies, only NSCLC adenocarcinoma was investigated. The overall objectives were to (i) determine whether individual or combinations of metabolites could be used as a diagnostic test to distinguish NSCLC adenocarcinoma from controls and (ii) to determine which, plasma or serum, provides more accurate classifiers for the detection of lung cancer. We developed individual and multimetabolite classifiers using a training test from the ADC1 study and evaluated the performance of the constructed classifiers, individually or in combination, in an independent test/validation study (ADC2). This study shows the potential of metabolite-based diagnostic tests for detection of lung adenocarcinoma. Further validation in a larger pool of samples is warranted.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
EMAIL
ofiehn@ucdavis.edu
PHONE
(530) 754-8258
STUDY_COMMENTS
SS = Sigma sample and is used as a quality control The first set (ADC1) used for biomarker development consisted of serum and plasma samples obtained from 52 stages I–IV NSCLC adenocarcinoma patients (52 plasma and 49 serum), and 31 healthy controls (31 pairs of serum and plasma) for a total of 163 samples. This set was regarded as the training set for biomarker discovery and classifier development. A second, independent case–control study (ADC2) consisting of serum and plasma samples collected from 43 stage I–IV NSCLC adenocarcinoma patients and 43 healthy controls (total 172 samples) was used as an independent test set for biomarker evaluation. A limitation of this study is the relatively small sample size for each cohort (52 cases, 31 controls for ADC1, and 43 cases and 43 controls for ADC2) because patient variability can be a big factor in smaller studies.
Mice were run for 15 minutes on a treadmill and then mice were induced into anesthesia at a dose of 5% isoflurane, then maintained by continuous inhalation of 2% isoflurane. Quadriceps muscle was collected first and flash frozen in liquid nitrogen. Then blood was collected from the left ventricle of the heart and placed into serum separating tubes. Blood was allowed to clot for 40 minutes and centrifuged, the supernatant was frozen in liquid nitrogen
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Facilities Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Mice were run for 15 minutes on a treadmill and then mice were induced into anesthesia at a dose of 5% isoflurane, then maintained by continuous inhalation of 2% isoflurane. Quadriceps muscle was collected first and flash frozen in liquid nitrogen. Then blood was collected from the left ventricle of the heart and placed into serum separating tubes. Blood was allowed to clot for 40 minutes and centrifuged, the supernatant was frozen in liquid nitrogen
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
We use ChAT(BAC)-EGFP mice, which express enhanced green fluorescent protein (EGFP) under the control of transcriptional regulatory elements for choline acetyltransferase (ChAT), the sole enzyme that catalyzes the biosynthesis of acetylcholine (ACh). These mice were treated with inducers of ChAT. Kidney were rapidly removed, frozen on liquid nitrogen and stored at -80C
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Rats were treated with donepezil (DPZ) after the induction of a model of glomerulonephritis (GN) to increase kidney ACh levels. Rats were euthanized at day 25 after the induction of the disease. Kidneys were rapidly removed, frozen in liquid nitrogen and stored at -80C
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
2 hydroxiglutarate with with IDH1-R132H inhibitor in neurospheres
STUDY_TYPE
Regular
STUDY_SUMMARY
Tumor neurospheres carrying genetic lession NPI (NRAS, shP53, IDH1-R132H) colony 1 and 2 (C1 and C2); NPAI (NRAS, shP53, shATRX, IDH1-R132H) colony 1 and 2 (C1 and C2); and NPA (NRAS, shP53, shATRX) (C1 and C2). Was treated with IDH1-R132H inhibitor. By 2HG assay we want to check the effect of the inhibitor in our cells.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
EMAIL
mkachman@med.umich.edu
PHONE
(734) 232-8175
NUM_GROUPS
3
TOTAL_SUBJECTS
12
STUDY_COMMENTS
(shATRX) : ATRX knockdown sequence into a Sleeping Beauty (SB) transposase-responsive plasmid
This West Coast Metabolomics Center sponsored pilot grant goal is to identify and validate interstitial cystitis/painful bladder syndrome (IC/PBS)-associated urinary metabolites. Our central hypothesis is that IC/PBS-associated metabolites in the urine of IC/PBS patients can segregate patients from control subjects, and that their levels are correlated with clinical symptoms. To test this hypothesis, we will identify IC/PBS-associated metabolites in urine using two independent platforms, GC-MS and quadrupole time-of-flight (Q-TOF) mass spectrometry under the collaboration with UC Davis WCMC scientists. We believe that this study will provide a significant potential clinical impact because results may lead to clinical methods to increase diagnostic accuracy and an improved understanding of the molecular basis of IC/PBS and its relationship to urologic conditions with overlapping symptoms.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
This West Coast Metabolomics Center sponsored pilot grant goal is to identify and validate interstitial cystitis/painful bladder syndrome (IC/PBS)-associated urinary metabolites. Our central hypothesis is that IC/PBS-associated metabolites in the urine of IC/PBS patients can segregate patients from control subjects, and that their levels are correlated with clinical symptoms. To test this hypothesis, we will identify IC/PBS-associated metabolites in urine using two independent platforms, GC-MS and quadrupole time-of-flight (Q-TOF) mass spectrometry under the collaboration with UC Davis WCMC scientists. We believe that this study will provide a significant potential clinical impact because results may lead to clinical methods to increase diagnostic accuracy and an improved understanding of the molecular basis of IC/PBS and its relationship to urologic conditions with overlapping symptoms.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
Health Sciences Drive, Davis, California, 95616, USA
Changes in the metabalome and lipidome in response to exercise training
STUDY_TYPE
HERITAGE (HEalth, RIsk factors, exercise Training And GEnetics) family study
STUDY_SUMMARY
The overall objective of the Heritage Family Study is to study the role of the genotype in cardiovascular, metabolic, and hormonal responses to aerobic exercise training and the contribution of regular exercise to changes in several cardiovascular disease and diabetes risk factors. The study cohort used in this analysis was derived from the pool of 473 Caucasian subjects (230 male and 243 female) from 99 nuclear families who completed ≥58 of the prescribed 60 exercise-training sessions. Utilizing a subsample of this Caucasian cohort, we selected family members from the Quebec center (N=125) to assess the metabolome and lipidome of circulating plasma under two well-defined environmental conditions, the pre- and post-training conditions.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
Health Sciences Drive, Davis, California, 95616, USA
Serum phosphatidylethanolamine levels distinguish benign from malignant solitary pulmonary nodules and represent a potential diagnostic biomarker for lung cancer (part I)
STUDY_SUMMARY
Recent computed tomography (CT) screening trials showed that it is effective for early detection of lung cancer, but were plagued by high false positive rates. Additional blood biomarker tests designed to complement CT screening and reduce false positive rates are highly desirable. In the current study, we expand upon our initial experimental findings as part of the discovery phase by evaluating metabolites in serum from subjects with benign or malignant SPNs using a combined approach of gas chromatography time-of-flight mass spectrometry (GC-TOFMS) and hydrophilic liquid chromatography accurate mass quadrupole time-of-flight mass spectrometry (HILIC-qTOFMS). Furthermore, we evaluated serum collected pre-diagnosis and at-diagnosis of lung cancer in addition to samples obtained post-surgical intervention from subjects with malignant SPNs (post-diagnosis). We hypothesize that our systems biology approach to identify candidate metabolomics biomarkers will ultimately lead to improved early detection of lung cancer and can be used in as a companion blood test to LDCT screening.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
Serum phosphatidylethanolamine levels distinguish benign from malignant solitary pulmonary nodules and represent a potential diagnostic biomarker for lung cancer (part II)
STUDY_SUMMARY
Recent computed tomography (CT) screening trials showed that it is effective for early detection of lung cancer, but were plagued by high false positive rates. Additional blood biomarker tests designed to complement CT screening and reduce false positive rates are highly desirable. In the current study, we expand upon our initial experimental findings as part of the discovery phase by evaluating metabolites in serum from subjects with benign or malignant SPNs using a combined approach of gas chromatography time-of-flight mass spectrometry (GC-TOFMS) and hydrophilic liquid chromatography accurate mass quadrupole time-of-flight mass spectrometry (HILIC-qTOFMS). Furthermore, we evaluated serum collected pre-diagnosis and at-diagnosis of lung cancer in addition to samples obtained post-surgical intervention from subjects with malignant SPNs (post-diagnosis). We hypothesize that our systems biology approach to identify candidate metabolomics biomarkers will ultimately lead to improved early detection of lung cancer and can be used in as a companion blood test to LDCT screening.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
The circadian oscillator in Synechococcus elongatus controls metabolite partitioning during diurnal growth (part II)
STUDY_SUMMARY
Cyanobacteria are increasingly being considered for use in large-scale outdoor production of fuels and industrial chemicals. Cyanobacteria can anticipate daily changes in light availability using an internal circadian clock and rapidly alter their metabolic processes in response to changes light availability. Understanding how signals from the internal circadian clock and external light availability are integrated to control metabolic shifts will be important for engineering cyanobacteria for production in natural outdoor environments. This study has assessed how “knowing” the correct time of day, via the circadian clock, affects metabolic changes when a cyanobacterium goes through a dark-to-light transition. Our data show that the circadian clock plays an important role in inhibiting activation of the oxidative pentose phosphate pathway in the morning. Synechococcus elongatus PCC 7942 is a genetically tractable model cyanobacterium that has been engineered to produce industrially relevant biomolecules and is the best-studied model for a prokaryotic circadian clock. However, the organism is commonly grown in continuous light in the laboratory, and data on metabolic processes under diurnal conditions are lacking. Moreover, the influence of the circadian clock on diurnal metabolism has been investigated only briefly. Here, we demonstrate that the circadian oscillator influences rhythms of metabolism during diurnal growth, even though light–dark cycles can drive metabolic rhythms independently. Moreover, the phenotype associated with loss of the core oscillator protein, KaiC, is distinct from that caused by absence of the circadian output transcriptional regulator, RpaA (regulator of phycobilisome-associated A). Although RpaA activity is important for carbon degradation at night, KaiC is dispensable for those processes. Untargeted metabolomics analysis and glycogen kinetics suggest that functional KaiC is important for metabolite partitioning in the morning. Additionally, output from the oscillator functions to inhibit RpaA activity in the morning, and kaiC-null strains expressing a mutant KaiC phosphomimetic, KaiC-pST, in which the oscillator is locked in the most active output state, phenocopies a ΔrpaA strain. Inhibition of RpaA by the oscillator in the morning suppresses metabolic processes that normally are active at night, and kaiC-null strains show indications of oxidative pentose phosphate pathway activation as well as increased abundance of primary metabolites. Inhibitory clock output may serve to allow secondary metabolite biosynthesis in the morning, and some metabolites resulting from these processes may feed back to reinforce clock timing.
INSTITUTE
UC Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
Health Sciences Drive, Davis, California, 95616, USA
EMAIL
ofiehn@ucdavis.edu
PHONE
(530) 754-8258
STUDY_COMMENTS
The first 4 samples were a test run to see how efficient the analysis was and were run on a lipidomics platform. The next 12 samples were the used in the paper and were the same as the original 4 samples, but they were split into 3 biological replicates and run on the GC platform.
Metabolic profiling of maternal urine can aid clinical management of Gestational Diabetes Mellitus (GDM)
STUDY_TYPE
Search for non-treated and treated GDM biomarkers in urine
STUDY_SUMMARY
NMR metabolomics study of maternal urine of 1) GDM women at the time of diagnosis and before treatment, to define the urine metabolic profile of untreated GDM, and of 2) GDM women treated using diet control alone or with the addition of insulin, to identify treatment-resistant and treatment-responsive metabolic pathways and, hence, evaluate treatment efficacy, and 3) GDM treatment prediction at the time of diagnosis, with the aim of finding potential predictive markers of future treatment requirements based on each individual metabotype.
INSTITUTE
University of Aveiro
DEPARTMENT
CICECO-Department of Chemistry, University of Aveiro
LAST_NAME
Gil
FIRST_NAME
Ana
ADDRESS
CICECO-Department of Chemistry, University of Aveiro
Noninvasive Recognition and Biomarkers of Early Allergic Asthma in Cats using Multivariate Statistics of NMR Spectra of Exhaled Breath Condensate
STUDY_TYPE
Statistical Analysis of NMR spectra of EBC samples
STUDY_SUMMARY
Asthma is prevalent in children and cats, and needs means of noninvasive diagnosis. We sought to distinguish noninvasively the differences in 53 cats before and soon after induction of allergic asthma, using NMR spectra of exhaled breath condensate (EBC). Statistical pattern recognition was improved by preprocessing the spectra with glog transformation. Classification of the 106 preprocessed spectra by principal component analysis, partial least squares with discriminant analysis (PLS-DA), and multi-level PLS-DA appears to be impaired by variances unrelated to eosinophilic asthma. By subtracting out confounding variances, orthogonal signal correction (OSC) PLS-DA greatly improved the separation of the healthy and early asthmatic states, attaining 94% specificity and 71% sensitivity in predictions. OSC-PLS-DA results highlight the elevation of acetone in two-thirds of the cats with early asthma. Asthma also decreased at least a dozen compounds, especially carboxylic acids such as short chain fatty acids and amino acids. These trends suggest that a majority of the cats with allergic asthma underwent alteration of metabolic fluxes through pyruvate and acetyl-CoA to promote ketosis. The noninvasive detection of early experimental asthma, its biomarkers in EBC, and metabolic rerouting invite further investigation of the diagnostic potential in humans.
INSTITUTE
University of Missouri-Columbia
DEPARTMENT
Department of Biochemistry, Department of Veterinary Medicine and Surgery
LABORATORY
Van Doren Lab & Reinero Lab
LAST_NAME
Van Doren
FIRST_NAME
Steven
ADDRESS
117 Schweitzer Hall, Biochemistry Department, University of Missouri-Columbia, Columbia, MO 65211
The goal of this study was to identify metabolic differences between 6 week old and 1 year old infants that have been potentially exposed to arsenic in order to determine its effect on the microbiome and the immune system.
ms3076 T1D poor glycemic control and control samples
STUDY_TYPE
Plasma metabolites in T1 diabetes
STUDY_SUMMARY
The objective of the study was to determine whether T1D with good glycemic control have persistent abnormalities of metabolites and pathways that exist in T1D with poor glycemic control.
Type 1 Diabetes good glycemic control and controls samples
STUDY_TYPE
Plasma metabolites in T1 diabetes
STUDY_SUMMARY
The objective of the study was to determine whether T1D with good glycemic control have persistent abnormalities of metabolites and pathways that exist in T1D with poor glycemic control.
Metabolomics Approach to Allograft Assessment in Liver Transplantation
STUDY_TYPE
Retrospective analysis of biobanked liver tissue from organ donors
STUDY_SUMMARY
This pilot study is designed to apply several types of metabolomic analysis for liver allograft assessment with the aim of identifying candidate biomarkers for allograft function and to develop a methodology that could be applied to larger scale studies. The three main categories of metabolomic analysis are reflected in each of the specific aims, including a targeted profiling of central carbon metabolism, open lipidomic and metabolomic profiling for hypothesis generation and MALDI-IMS for tissue-based spatial analysis. Each of these approaches offers potential benefits that could be optimized in a protocol for larger scale studies depending the results of the pilot investigations.
targeted metabolomics of gastrocnemius tissue samples obtained from 6 month old (adult) mice- Both Sham and after inducing lung injury
STUDY_TYPE
targeted metabolomic analysis
STUDY_SUMMARY
Introduction: Older patients are more likely to acquire and die from acute respiratory distress syndrome (ARDS) and muscle weakness may be more significant in older survivors. Recent data implicate muscle ring finger protein 1 (MuRF1) in lung injury-induced skeletal muscle atrophy in young mice and identify an alternative role for MuRF1 in cardiac metabolism regulation through inhibition of fatty acid oxidation. Objectives: To develop a model of lung injury-induced muscle wasting in old mice and to evaluate the skeletal muscle metabolomic profile of adult and old acute lung injury (ALI) mice. Methods: Young (2 month), adult (6 month) and old (20 month) male C57Bl6J mice underwent Sham (intratracheal H2O) or ALI [intratracheal E. coli lipopolysaccharide (i.t. LPS)] conditions and muscle functional testing. Metabolomic analysis on gastrocnemius muscle was performed using gas chromatography-mass spectrometry (GC-MS). Results: Old ALI mice had increased mortality and failed to recover skeletal muscle function compared to adult ALI mice. Muscle MuRF1 expression was increased in old ALI mice at day 3. Non-targeted muscle metabolomics revealed alterations in amino acid biosynthesis and fatty acid metabolism in old ALI mice. Targeted metabolomics of fatty acid intermediates (acyl-carnitines) and amino acids revealed a reduction in long chain acyl-carnitines in old ALI mice. Conclusion: This study demonstrates age-associated susceptibility to ALI-induced muscle wasting which parallels a metabolomic profile suggestive of altered muscle fatty acid metabolism. MuRF1 activation may contribute to both atrophy and impaired fatty acid oxidation, which may synergistically impair muscle function in old ALI mice.
INSTITUTE
University of North Carolina, Duke University
DEPARTMENT
UNC McAllister Heart Institute, Duke Molecular Physiology Institute
LABORATORY
Multiple Centers
LAST_NAME
Willis, Ilaiwy
FIRST_NAME
Monte, Amro
ADDRESS
111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA
Targeted metabolomics of gastrocnemius tissue samples obtained from 20 month old (old) mice- Both Sham and after inducing lung injury (part II)
STUDY_TYPE
Targeted metabolomic analysis
STUDY_SUMMARY
Introduction: Older patients are more likely to acquire and die from acute respiratory distress syndrome (ARDS) and muscle weakness may be more significant in older survivors. Recent data implicate muscle ring finger protein 1 (MuRF1) in lung injury-induced skeletal muscle atrophy in young mice and identify an alternative role for MuRF1 in cardiac metabolism regulation through inhibition of fatty acid oxidation. Objectives: To develop a model of lung injury-induced muscle wasting in old mice and to evaluate the skeletal muscle metabolomic profile of adult and old acute lung injury (ALI) mice. Methods: Young (2 month), adult (6 month) and old (20 month) male C57Bl6J mice underwent Sham (intratracheal H2O) or ALI [intratracheal E. coli lipopolysaccharide (i.t. LPS)] conditions and muscle functional testing. Metabolomic analysis on gastrocnemius muscle was performed using gas chromatography-mass spectrometry (GC-MS). Results: Old ALI mice had increased mortality and failed to recover skeletal muscle function compared to adult ALI mice. Muscle MuRF1 expression was increased in old ALI mice at day 3. Non-targeted muscle metabolomics revealed alterations in amino acid biosynthesis and fatty acid metabolism in old ALI mice. Targeted metabolomics of fatty acid intermediates (acyl-carnitines) and amino acids revealed a reduction in long chain acyl-carnitines in old ALI mice. Conclusion: This study demonstrates age-associated susceptibility to ALI-induced muscle wasting which parallels a metabolomic profile suggestive of altered muscle fatty acid metabolism. MuRF1 activation may contribute to both atrophy and impaired fatty acid oxidation, which may synergistically impair muscle function in old ALI mice.
INSTITUTE
University of North Carolina, Duke University
DEPARTMENT
UNC McAllister Heart Institute, Duke Molecular Physiology Institute
LABORATORY
Multiple Centers
LAST_NAME
Willis, Ilaiwy
FIRST_NAME
Monte, Amro
ADDRESS
111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA
Targeted metabolomics of MuRF1 overexpressing cardiomyocytes compared to their wildtype controls (part I)
STUDY_TYPE
Targeted metabolomic analysis
STUDY_SUMMARY
The transcriptional regulation of peroxisome proliferator-activated receptor (PPAR) a by post-translational modification, such as ubiquitin, has not been described. We report here for the first time an ubiquitin ligase (muscle ring finger-1/MuRF1) that inhibits fatty acid oxidation by inhibiting PPARa, but not PPARß/d or PPAR? in cardiomyocytes in vitro. Similarly, MuRF1 Tg+ hearts showed significant decreases in nuclear PPARa activity and acyl-carnitine intermediates, while MuRF1-/- hearts exhibited increased PPARa activity and acyl-carnitine intermediates. MuRF1 directly interacts with PPARa, mono-ubiquitinates it, and targets it for nuclear export to inhibit fatty acid oxidation in a proteasome independent manner. We then identified a previously undescribed nuclear export sequence in PPARa, along with three specific lysines (292, 310, 388) required for MuRF1's targeting of nuclear export. These studies identify the role of ubiquitination in regulating cardiac PPARa, including the ubiquitin ligase that may be responsible for this critical regulation of cardiac metabolism in heart failure.
INSTITUTE
University of North Carolina
DEPARTMENT
McAllister Heart Institute, Department of Internal Medicine
LABORATORY
Multiple Centers
LAST_NAME
Willis
FIRST_NAME
Monte
ADDRESS
111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA
Targeted metabolomics of MuRF1 Knockdown cardiomyocytes compared to their wildtype controls (part 2)
STUDY_TYPE
Targeted metabolomic analysis
STUDY_SUMMARY
The transcriptional regulation of peroxisome proliferator-activated receptor (PPAR) α by post-translational modification, such as ubiquitin, has not been described. We report here for the first time an ubiquitin ligase (muscle ring finger-1/MuRF1) that inhibits fatty acid oxidation by inhibiting PPARα, but not PPARβ/δ or PPARγ in cardiomyocytes in vitro. Similarly, MuRF1 Tg+ hearts showed significant decreases in nuclear PPARα activity and acyl-carnitine intermediates, while MuRF1−/− hearts exhibited increased PPARα activity and acyl-carnitine intermediates. MuRF1 directly interacts with PPARα, mono-ubiquitinates it, and targets it for nuclear export to inhibit fatty acid oxidation in a proteasome independent manner. We then identified a previously undescribed nuclear export sequence in PPARα, along with three specific lysines (292, 310, 388) required for MuRF1s targeting of nuclear export. These studies identify the role of ubiquitination in regulating cardiac PPARα, including the ubiquitin ligase that may be responsible for this critical regulation of cardiac metabolism in heart failure.
INSTITUTE
University of North Carolina
DEPARTMENT
McAllister Heart Institute, Department of Internal Medicine
LABORATORY
Multiple Centers
LAST_NAME
Willis
FIRST_NAME
Monte
ADDRESS
111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA
Quantitative measurements of vitamin D in T1D poor control, good control, and controls.
STUDY_TYPE
Quantitative measurements of vitamin D
STUDY_SUMMARY
The objective of the study was to determine whether T1D with good glycemic control have persistent abnormalities of metabolites and pathways that exist in T1D with poor glycemic control.
Plasma sphingolipid changes with autopsy-confirmed Lewy body or Alzheimer's pathology
STUDY_TYPE
targeted sphingolipid and fatty acid analyses
STUDY_SUMMARY
We identified four groups with available plasma 2 years before death: high (n = 12) and intermediate-likelihood DLB (n = 14) based on the third report of the DLB consortium; dementia with Alzheimer's pathology (AD; n = 18); and cognitively normal with normal aging pathology (n = 21). Lipids were measured using ESI/MS/MS.
Quantitative measurements of free fatty acid in T1D poor control, good control, and controls.
STUDY_TYPE
Quantitative measurements of free fatty acid
STUDY_SUMMARY
The objective of the study was to determine whether T1D with good glycemic control have persistent abnormalities of metabolites and pathways that exist in T1D with poor glycemic control.
Quantitative measurements of amino acids in T1D poor control, good control, and controls.
STUDY_TYPE
Quantitative measurements of amino acid
STUDY_SUMMARY
The objective of the study was to determine whether T1D with good glycemic control have persistent abnormalities of metabolites and pathways that exist in T1D with poor glycemic control.
Characterizing commonalities and differences between the breast and prostate cancer metabotypes in African-American cohorts (part I)
STUDY_TYPE
Identify Breast Cancer Progression and Prostate Cancer correlative Metabolite Markers
STUDY_SUMMARY
Thus, we aimed to 1) understand mechanisms related to the onset and progression of BCa, 2) identify precursors and targets for prevention and therapy for each stage, grade and subtype which may contribute to the disparate impact of BCa in African American women, and 3) Identify common and different BCa metabolite markers versus PCa markers.
Characterizing commonalities and differences between the breast and prostate cancer metabotypes in African-American cohorts
STUDY_TYPE
Identify Breast Cancer Progression and Prostate Cancer correlative Metabolite Markers
STUDY_SUMMARY
Thus, we aimed to 1) understand mechanisms related to the onset and progression of BCa, 2) identify precursors and targets for prevention and therapy for each stage, grade and subtype which may contribute to the disparate impact of BCa in African American women, and 3) Identify common and different BCa metabolite markers versus PCa markers.
Metabotypes of Subjects with Adverse Reactions Following Vaccination
STUDY_TYPE
Metabolomic Profile of Human Serum
STUDY_SUMMARY
Metabolomics may help identify a particular metabolic signature “metabotype” in patients who are predisposed to developing AEFI such as a systemic reaction, or myocarditis that currently is difficult or impossible to identify prior to the development of the AEFI. This proposed pilot study looks at the metabolic profiles of a specific population of subjects who received the smallpox vaccine with or without other concomitantly administered vaccines to help determine if a unique metabotype can be identified in subjects who reported systemic reactions following immunization. In addition, this proposed study will look at the metabolic profile of several subjects with subclinical or clinically diagnosed myopericarditis to determine if these subjects have a unique metabotype. The ability to identify a unique metabotype would allow a clinician to potentially mitigate serious AEFI and ultimately improve the quality of immunization healthcare. If identified, these profiles might represent novel biomarkers of risk that can supplement existing clinical decision making for risk stratification or vaccine exemptions.
Metabolomic Profiling of the Malaria Box Reveals Antimalarial Target Pathways
STUDY_SUMMARY
Here we interrogated the in vitro metabolic effects of 189 drugs (including 169 of the drug-like compounds from the Malaria Box) using ultra-high performance liquid chromatography mass-spectrometry (UHPLC-MS). The resulting metabolic fingerprints provide information on the parasite biochemical pathways affected by pharmacologic intervention and offer a critical blueprint for selecting and advancing lead compounds as next-generation antimalarial drugs. Our results reveal several major classes of metabolic disruption, which allow us to predict the mode-of-action (MoA) for many of the Malaria Box compounds.
INSTITUTE
Penn State University
LAST_NAME
Llinas
FIRST_NAME
Manuel
ADDRESS
W126 Millenium Science Complex, University Park, PA 16802
Metabolomics Analysis of Triple Negative Breast Cancer (BCa) Cell Lines
STUDY_TYPE
Metabolomics comparison of different breast cancer cell lines
STUDY_SUMMARY
We used untargeted metabolomic profiling to distinguish this form of BCa from estrogen receptor positive (ER+) subtypes (+/- HER2/neu) and determine that may explain why a commonly used chemotherapeutic, paclitaxel, is generally ineffective at eliciting long-term cytotoxic and/or cytostatic responses in cell line models of TNBC. This metabolomics study used broad spectrum 1H NMR to compare Luminal A (BT474, MCF-7) and triple-negative (MDA-MB-231, MDA-MB-468) BCa cell lines, to determine differences in the two subtypes as well as distinguish therapeutic treatment responses for identifying new targets for drug discovery.
INSTITUTE
RTI International
DEPARTMENT
Discovery Sciences
LABORATORY
STS/RCMRC
LAST_NAME
Sumner
FIRST_NAME
Susan
ADDRESS
3040, East Cornwallis Road, Research Triangle Park, NC 27709
EMAIL
ssumner@rti.org
PHONE
919-541-7479
NUM_GROUPS
4
TOTAL_SUBJECTS
24
NUM_MALES
N/A
NUM_FEMALES
N/A
STUDY_COMMENTS
4 breast cancer cell lines, treated with paclitaxel compared to controls (3 replicates/line/condition)
PUBLICATIONS
J. Proteome Res., Article ASAP, DOI: 10.1021/acs.jproteome.6b00430
Quantitative measurements of TCA cycle metabolites in T1D poor control, good control, and controls.
STUDY_TYPE
Quantitative measurements of plasma levels of tricarboxylic acid (TCA) cycle metabolites
STUDY_SUMMARY
The objective of the study was to determine whether T1D with good glycemic control have persistent abnormalities of metabolites and pathways that exist in T1D with poor glycemic control.
Utilizing Metabolomics to Understand Novel Anti-Desmoid Tumor Drugs
STUDY_SUMMARY
This pilot study will use broad spectrum metabolomics to study the tumorigenesis process of fibroblasts to desmoids by investigating paired desmoid and fibroblast cell lines, in addition to unaffected fibroblast cells. Additionally, this pilot study will explore the effects of two of the active drugs identified on the desmoid and fibroblast cells.
Utilizing Metabolomics to Understand Novel Anti-Desmoid Tumor Drugs
STUDY_SUMMARY
This pilot study will use broad spectrum metabolomics to study the tumorigenesis process of fibroblasts to desmoids by investigating paired desmoid and fibroblast cell lines, in addition to unaffected fibroblast cells. Additionally, this pilot study will explore the effects of two of the active drugs identified on the desmoid and fibroblast cells.
CNS and peripheral metabolomics of calorie restriction in a mouse model of Alzheimer’s disease (part I)
STUDY_SUMMARY
This pilot metabolomic study will evaluate brain specimens from an established mouse model of AD, the tq2576 mouse model of cerebral amyloid overexpression (APP), in comparison to their non-transgenic (NTG) littermates. These animals were either on a CR or ad libitum (AL) diet, and specimens were collected at two time points (5 and 15 months of age). Tissue from this cohorts of mice have already undergone microbiome analysis, and await coordinated brain and peripheral tissue assessments. Future analysis will include metabolomics, RNA-seq, and microarray data to assess the gut-brain microbiome system in neurodegenerative disorders.
CNS and peripheral metabolomics of calorie restriction in a mouse model of Alzheimer’s disease (part II)
STUDY_SUMMARY
This pilot metabolomic study will evaluate cecal specimens from an established mouse model of AD, the tq2576 mouse model of cerebral amyloid overexpression, in comparison to their non-transgenic (ntg) littermates. These animals were either on a CR or ad libitum (AL) diet, and specimens were collected at two time points (5 and 15 months of age). Tissue from this cohorts of mice have already undergone microbiome analysis, and await coordinated brain and peripheral tissue assessments. Future analysis will include metabolomics, RNA-seq, and microarray data to assess the gut-brain microbiome system in neurodegenerative disorders.
Transpulmonary metabolomics in pulmonary arterial hypertension
STUDY_SUMMARY
We hypothesize that transpulmonary metabolomic profiling will demonstrate a PAH-specific metabolic signature. We will examine organ-specific metabolism by measuring blood flowing into (pulmonary artery) and out of (pulmonary artery wedge) the pulmonary circulation at the time of right heart catheterization (RHC). We will compare PAH to patients without PH and to a disease control cohort with PH due to left heart disease (pulmonary ventrical hypertension - PVH).
Metabolomics of Saliva Samples Obtained from Subjects with Diabetes
STUDY_SUMMARY
In this research, were are investigating the metabolic profile changes associated with well- and poorly-controlled type 1 and 2 diabetes and if there are distinct metabolite compounds that may be associated with glycemic control. The PI of the study collected whole unstimulated saliva samples were from subjects with well- and poorly-controlled type 1 and type 2 diabetes. Subjects were selected based on the level of A1C (<7= well-controlled and >7 = poorly controlled). Saliva samples were shipped to RTI RCMRC for a broad spectrum reverse phase metabolomics analysis.
Effect of a complex matrix on the degradation of nucleotide triphosphates
STUDY_TYPE
Comparison of degradation kinetics
STUDY_SUMMARY
The effect of a complex cellular matrix extracted from yeast (S. cerevisiae, strain YSBN6 (MATa; genotype: FY3 ho::HphMX4 derived from the S288C parental strain)) on the degradation profiles of nucleotide triphosphates extracted under typical boiling ethanol conditions was evaluated.
INSTITUTE
University of Groningen
DEPARTMENT
Analytical Biochemistry
LAST_NAME
Bischoff
FIRST_NAME
Rainer
ADDRESS
Antonius Deusinglaan 1 (XB20), Building 3226, room 601, 9713 AV Groningen, The Netherlands
Effect of the culture medium on the degradation of nucleotide triphosphates
STUDY_TYPE
Endpoint measurement
STUDY_SUMMARY
The effect of the Verduyn culture medium on the degradation profiles of nucleotide triphosphates extracted under typical boiling ethanol conditions was evaluated.
INSTITUTE
University of Groningen
DEPARTMENT
Analytical Biochemistry
LAST_NAME
Bischoff
FIRST_NAME
Rainer
ADDRESS
Antonius Deusinglaan 1 (XB20), Building 3226, room 601, 9713 AV Groningen, The Netherlands
Amino Acid Quantifcation of obese patients on a 16 week caloric restriction from muscle biopsy (part II)
STUDY_TYPE
timecourse, quantitative measurements of amino acid
STUDY_SUMMARY
Caloric restriction (CR) improves insulin sensitivity and reduces the incidence of diabetes in obese individuals. The underlying mechanisms whereby CR improves insulin sensitivity are not clear. We evaluated the effect of 16 weeks of CR on whole-body insulin sensitivity by pancreatic clamp before and after CR in 11 obese participants (BMI = 35 kg/m2) compared with 9 matched control subjects (BMI = 34 kg/m2). Compared with the control subjects, CR increased the glucose infusion rate needed to maintain euglycemia during hyperinsulinemia, indicating enhancement of peripheral insulin sensitivity. This improvement in insulin sensitivity was not accompanied by changes in skeletal muscle mitochondrial oxidative capacity or oxidant emissions, nor were there changes in skeletal muscle ceramide, diacylglycerol, or amino acid metabolite levels. However, CR lowered insulin-stimulated thioredoxin-interacting protein (TXNIP) levels and enhanced nonoxidative glucose disposal. These results support a role for TXNIP in mediating the improvement in peripheral insulin sensitivity after CR.
Impacts of high-fat diet (HFD), high-carbohydrate diet (HCD) and high-fat-high-carbohydrate diet (HFHCD) on metabolites in a farmed cyprinid fish Megalobrama amblycephala.
STUDY_TYPE
Dietary imbalance experiment
STUDY_SUMMARY
1H NMR-based metabolomic approach to measure the concentrations of metabolites in plasma and liver of four different diet groups: HFD, HCD, HFHCD and control. Multivariate statistical analyses were used to determine significantly changed metabolites between all group-pairs.
Metabolomic profiles along the gastrointestinal tract of the healthy dog
STUDY_SUMMARY
Introduction: The fecal microbiome is relevant to the health and disease of many species. The importance of the fecal metabolome has more recently been appreciated, but our knowledge of the microbiome and metabolome at other sites along the gastrointestinal tract remains deficient. Objective: To analyze the gastrointestinal microbiome and metabolome of healthy domestic dogs at four anatomical sites. Methods: Samples of the duodenal, ileal, colonic, and rectal contents were collected from six adult dogs after humane euthanasia for an unrelated study. The microbiota were characterized using Illumina sequencing of 16S rRNA genes. The metabolome was characterized by mass spectrometry-based methods. Results: Prevalent phyla throughout the samples were Proteobacteria, Firmicutes, Fusobacteria, and Bacteroidetes, consistent with previous findings in dogs and other species. A total of 530 unique metabolites were detected; 199 of these were identified as previously named compounds, but 141 of them had at least one significantly different site-pair comparison. Noteworthy examples include amino acids, which decreased from the small to large intestine; pyruvate, which was at peak concentrations in the ileum; and several phenol-containing carboxylic acid compounds that increased in the large intestine. Conclusion: The microbiome and metabolome vary significantly at different sites along the canine gastrointestinal tract.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
Weight loss and weight maintenance obtained with or without GLP-1 analogue treatment decrease branched chain amino acid levels.
STUDY_TYPE
RCT
STUDY_SUMMARY
RCT of the effect og liraglutide on weight maintenance. 58 individuals wer included and subjected to low calorie intake during 8 weeks. Individuals lost a mean of 12 kg during that period. Individuals were then randomized to receive 1.2 mg liraglutide daily for 1 year or serving as control. Metabolites were measured at inclusion (-8 weeks), randomization (0 weeks) and at 4 and 52 weeks during weight maintenance.
INSTITUTE
NNF Center for Metabolic Research
LAST_NAME
Engelbrechtsen
FIRST_NAME
Line
ADDRESS
Section of Metabolic Genetics, Universitetsparken 1, DIKU building 1st floor, 2100 Copenhagen
Understanding the response to endurance exercise using a systems biology approach: combining blood metabolomics, transcriptomics and miRNome in horses
STUDY_SUMMARY
Endurance exercise in horses implies adaptive processes involving affective, physiological, biochemical, and cognitive-behavioral response in an attempt to regain homeostasis. We hypothesized that the identification of the relationships between blood metabolome, transcriptome and miRNome during endurance exercise could provide significant insights into the molecular response to intense exercise or prediction of this response at basal status. In this perspective, the serum metabolome and whole-blood transcriptome and miRNome data were obtained from 10 horses before and after a 160 km endurance competition. Results: We obtained a global regulatory network based on 11 unique metabolites, 263 metabolic genes and 5 miRNAs whose expression was significantly altered at T1 (post- endurance competition) relative to T0 (baseline, pre- endurance competition). This network provided new insights into the cross talk between the distinct molecular pathways (e.g. energy and oxygen sensing, oxidative stress, and inflammation) that were not detectable when analyzing single metabolites or transcripts alone. This suggested that single metabolites and transcripts were carrying out multiple roles and thus sharing several biochemical pathways. Using a regulatory impact factor metric analysis, this regulatory network was further confirmed at the transcription factor and miRNA levels. In an extended cohort of 39 animals, multiple factor analysis confirmed the strong associations between lactate, methylene derivatives, miR-21-5p, miR-16-5p, and genes that coded proteins involved in metabolic reactions primarily related to energy, ubiquitin proteasome and lipopolysaccharide immune responses at T1. Multiple factorial analyses also identified potential biomarkers at T0 for an increased possibility of failure to finish an endurance competition.
Assessing metabolic changes to maternal rat liver tissue during and post-pregnancy (part II)
STUDY_SUMMARY
Assessing metabolic changes to maternal rat liver tissue during and post-pregnancy. Liver tissue was harvested post-mortem from rats or mice without pregnancy (Nulliparous - NP), time course during pregnancy in days (P2-4, P11-13m P18-20), lactation day 10 (LD10), in during involution of the liver (I2, I4, I6, I8, I10) and 4-weeks regression after preganancy (R4).
Determine how inhibition of autophagy/proteasome degradation or inhibition of protein synthesis in models of muscle insulin resistance affect amino acid metabolites
STUDY_SUMMARY
To determine which protein degradation pathways downstream of IR and IGF1R contribute to changes in amino acid and mitochondrial metabolite pools, we will treat control, M-IR-/-, MIGIRKO, and HFD obese mice with inhibitors of autophagy or proteasome. We will treat 5 animals each of control, M-IR-/-, MIGIRKO, and HFD mice with vehicle, colchicine to inhibit autophagy, or MG132 to inhibit proteasome activity, then measure amino acid in muscle tissue.
Investigating TCA concentrations in mice muscle tissue lacking insulin receptors and IGF-1 receptors
STUDY_SUMMARY
Quantitative measures of TCA cycle metabolites from control, M-IR-/-, M-IGF1R-/- , and MIGIRKO mice. Also compare mice on a chow diet to mice on a high fat diet (HFD).
Inhibition of autophagy/proteasome degradation or inhibition of protein synthesis in models of muscle insulin resistance affect TCA cycle
STUDY_SUMMARY
To determine which protein degradation pathways downstream of IR and IGF1R contribute to changes in amino acid and mitochondrial metabolite pools, we will treat control, M-IR-/-, MIGIRKO, and HFD obese mice with inhibitors of autophagy or proteasome. We will treat 5 animals each of control, M-IR-/-, MIGIRKO, and HFD mice with vehicle, colchicine to inhibit autophagy, or MG132 to inhibit proteasome activity, then measure TCA cycle in muscle tissue.
Inhibition of autophagy/proteasome degradation or inhibition of protein synthesis in models of muscle insulin resistance affect amino acids metabolites in serum
STUDY_SUMMARY
To determine which protein degradation pathways downstream of IR and IGF1R contribute to changes in amino acid and mitochondrial metabolite pools, we will treat control, M-IR-/-, MIGIRKO, and HFD obese mice with inhibitors of autophagy or proteasome. We will treat 5 animals each of control, M-IR-/-, MIGIRKO, and HFD mice with vehicle, colchicine to inhibit autophagy, or MG132 to inhibit proteasome activity, then measure amino acid metabolites in serum.
Metabolomics of longitudinal plasma samples from Macaca mulatta infected with Plasmodium cynomolgi B strain.
STUDY_TYPE
Longitudinal parasite infection and treatment of multiple individuals
STUDY_SUMMARY
Malaria-naive male rhesus macaques (Macaca mulatta), approximately three years of age, were inoculated intravenously with salivary gland sporozoites isolated at the Centers for Disease Control and Prevention from multiple Anopheles species (An. dirus, An. gambiae, and An. stephensi) and then profiled for parasitological, clinical, immunological, functional genomic, lipidomic, proteomic, and metabolomic measurements. The experiment was designed for 100 days, and pre- and post-100 day periods to prepare subjects and administer curative treatments respectively. The anti-malarial drug Artemether was subcuratively administered selectively to several subjects during the primary parasitemia to suppress clinical complications and to all animals for curative treatment of blood-stage infections to allow detection of relapses. One subject was euthanized during the 100-day experimental period due to clinical complications. The anti-malarial drugs Primaquine and Chloroquine were administered to all remaining subjects at the end of the study for curative treatment of the liver and blood-stage infections, respectively. Plasma samples were acquired every other day from capillary blood and during seven-time point collections of venous blood. Supplemental files, including a ReadMe with additional experimental details, all raw data, and analytical metadata, are provided as part of this submission.
INSTITUTE
Emory University
DEPARTMENT
School of Medicine, Vaccine Center at Yerkes
LAST_NAME
Karpuzoglu
FIRST_NAME
Ebru
ADDRESS
Emory University, 954 Gatewood Rd, Room 208, Atlanta, GA 30329
EMAIL
mahpic@emory.edu
PHONE
N/A
TOTAL_SUBJECTS
5
STUDY_COMMENTS
Malaria Host Pathogen Interaction Center Experiment 04, 5 subjects 286 samples, "The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC). These results are a product of a consortium of researchers known as the Malaria Host Pathogen Interaction Center (MaHPIC). For more information on the MaHPIC, please visit http://www.systemsbiology.emory.edu/ . Within the MaHPIC, these data were collected as part of 'Experiment 04' (E04). To access other publicly available results from E04 and other MaHPIC Experiments, including clinical results (specifics on drugs administered, diet, and veterinary interventions), and other omics, visit http://plasmodb.org/plasmo/mahpic.jsp . This page will be updated as datasets are released to the public."
Measuring amino acid metabolites in insulin resistant and insulin deficient mouse tissue models
STUDY_SUMMARY
To compare models of insulin resistance to a model of loss of insulin signaling, we will also determine amino acid metabolites from muscle, using control and streptozotocin (STZ) treated mice as a model of insulin deficient diabetes.
Measuring acylcarnitine concentrations in insulin resistant and insulin deficient mouse tissue models
STUDY_SUMMARY
To compare models of insulin resistance to a model of loss of insulin signaling, we will also determine muscle acylcarnitine concentrations, using control and streptozotocin (STZ) treated mice as a model of insulin deficient diabetes. Changes in metabolite profiles will be correlated with activation of mTOR and FoxO pathways in muscle.
Measuring ceramide concentrations in insulin resistant and insulin deficient mouse tissue models
STUDY_SUMMARY
To compare models of insulin resistance to a model of loss of insulin signaling, we will also determine ceramide concentration in muscle, using control and streptozotocin (STZ) treated mice as a model of insulin deficient diabetes.
Investigating ceremide concentrations in mice muscle tissue lacking insulin receptors and IGF-1 receptors
STUDY_SUMMARY
Quantitative measures of ceramide metabolite concentrations in muscle from control, M-IR-/-, M-IGF1R-/- , and MIGIRKO mice. Also compare mice on a chow diet to mice on a high fat diet (HFD).
Measuring TCA cycle concentrations in insulin resistant and insulin deficient mouse tissue models
STUDY_SUMMARY
To compare models of insulin resistance to a model of loss of insulin signaling, we will also determine TCA cycle metabolites in muscle, using control and streptozotocin (STZ) treated mice as a model of insulin deficient diabetes.
Measuring NEFA concentrations in insulin resistant and insulin deficient mouse tissue models
STUDY_SUMMARY
To compare models of insulin resistance to a model of loss of insulin signaling, we will also determine nonesterified fatty acid metabolites in muscle, using control and streptozotocin (STZ) treated mice as a model of insulin deficient diabetes.
Plasma metabolomics profiling for fish maturation in blunt snout bream
STUDY_TYPE
Metabolomics experiment
STUDY_SUMMARY
We investigated the comprehensive metabolic profiles of plasma among immature females, mature females ready to spawn, as well as already spawned breeders of blunt snout bream (Megalobrama amblycephala). The purpose of this study was to screen out potential biomarkers for sexual mature female M. amblycephala compared to immature female individuals and already spawned breeders. The three groups were set up in this study, including one year old immature females, 2 years old sexually mature females ready to spawning and successfully spawning females of M. amblycephala. The plasma samples were collected to investigate the comprehensive metabolic profiles through UPLC-MS/MS based metabolomics analysis method. According to multivariate and univariate statistical analysis, plasma metabolite profiles of three groups were obviously separated, and the plasma metabolite profiles of immature female M. amblycephala were much more different from mature females ready to spawn as well as already spawned breeders. The differential plasma metabolites from three hormone related pathways including GnRH signaling pathway, steroid hormone biosynthesis and steroid biosynthesis, were further analyzed. A total of 29 metabolites were identified as differential biomarkers associated with the female maturation status
INSTITUTE
Huazhong Agricultural University, Wuhan
DEPARTMENT
College of Fisheries
LABORATORY
Key Lab of Freshwater Animal Breeding, Ministry of Agriculture
Effects of Curcumin Supplementation on the Amino Acid Concentration of Older Adults: Relation to Vascular Function
STUDY_SUMMARY
Perform amino acid concentrations metabolite analysis related to nitric oxide biology, oxidative stress and inflammation in plasma before and after 12 weeks of oral curcumin (2000 mg/d) or placebo (double-blind, randomized) in men and women aged 45-79 years who are free from clinical cardiovascular disease.
INSTITUTE
Mayo Clinic
LAST_NAME
Seals
FIRST_NAME
Douglas
ADDRESS
Department of Integrative Physiology University of Colorado Boulder, CO 80309
Effects of Curcumin Supplementation on the Non‐Esterified Fatty Acids concentration of Older Adults: Relation to Vascular Function
STUDY_SUMMARY
Perform non-esterified fatty acid concentrations metabolite analysis related to nitric oxide biology, oxidative stress and inflammation in plasma before and after 12 weeks of oral curcumin (2000 mg/d) or placebo (double-blind, randomized) in men and women aged 45-79 years who are free from clinical cardiovascular disease.
INSTITUTE
Mayo Clinic
LAST_NAME
Seals
FIRST_NAME
Douglas
ADDRESS
Department of Integrative Physiology University of Colorado Boulder, CO 80309
Effects of Curcumin Supplementation on the Ceramides Concentration of Older Adults: Relation to Vascular Function
STUDY_SUMMARY
Perform ceramides concentrations metabolite analysis related to nitric oxide biology, oxidative stress and inflammation in plasma before and after 12 weeks of oral curcumin (2000 mg/d) or placebo (double-blind, randomized) in men and women aged 45-79 years who are free from clinical cardiovascular disease.
INSTITUTE
Mayo Clinic
LAST_NAME
Seals
FIRST_NAME
Douglas
ADDRESS
Department of Integrative Physiology University of Colorado Boulder, CO 80309
Effects of Curcumin Supplementation on the Acylcarnitine Concentration of Older Adults: Relation to Vascular Function
STUDY_SUMMARY
Perform acylcarnitine concentrations metabolite analysis related to nitric oxide biology, oxidative stress and inflammation in plasma before and after 12 weeks of oral curcumin (2000 mg/d) or placebo (double-blind, randomized) in men and women aged 45-79 years who are free from clinical cardiovascular disease.
INSTITUTE
Mayo Clinic
LAST_NAME
Seals
FIRST_NAME
Douglas
ADDRESS
Department of Integrative Physiology University of Colorado Boulder, CO 80309
Our aim is to identify the LSR-driven metabolomics profile of breast cancer cells in lean and obesogenic environments. Breast cancer cell models with high or undetectable levels of LSR, including drug resistance models, were cultured in lean and obesogenic environments and comprehensive metabolomics profiling, including lipidomics-focused sub-analyses were performed. The metabolomics analyses using both approaches will help us determine if LSR enhances aggressive breast cancer phenotypes via modulation of cellular bioenergetic metabolism, ultimately contributing to poor patient outcome.
Broad spectrum, reverse phase LCMS metabolomics (Negative ion mode)
STUDY_SUMMARY
Our aim is to identify the LSR-driven metabolomics profile of breast cancer cells in lean and obesogenic environments. Breast cancer cell models with high or undetectable levels of LSR, including drug resistance models, were cultured in lean and obesogenic environments and comprehensive metabolomics profiling, including lipidomics-focused sub-analyses were performed. The metabolomics analyses using both approaches will help us determine if LSR enhances aggressive breast cancer phenotypes via modulation of cellular bioenergetic metabolism, ultimately contributing to poor patient outcome.
Effects of herb DG and KK01 on Type 2 Diabetes Mellitus (T2DM) through Lipidomics
STUDY_TYPE
LC-MS lipidomics
STUDY_SUMMARY
According to the results in animal test, KK01 is effective in controlling blood glucose increase with comparable effect as metformin and rosiglitazone. This study will conduct lipid profile comparison for serum samples generated from the animal tests. The comparison will be based on the following groups: 1) db/db mice + DG-high dose; 2) db/db mice +DG-low dose; 3) db/db mice + KK01-high dose; 4) db/db mice + KK01-low dose; 5) db/db mice + metformin; 6) db/db mice + rosiglitazone; 7) db/db mice + saline (disease model); and 8) wild type mice + saline (healthy model). The determined lipid marker(s) will be applied to elucidate the drug target(s) and mechanisms of DG and KK01. Furthermore, comparison of target(s) between KK01 and the first line drugs in diabetic treatment, e.g., metformin and rosiglitazone, will facilitate the finding of featured pathway(s) of KK01 differentiated from the established drugs. Comparison of drug target(s) between KK01 and DG can help to understand the synergistic effects of multiple constituents in the herb.
Kidney tissue metabolomic profiling of diabetic nephropathy in the steptozotocin induced type-1 diabetes mouse model.
STUDY_TYPE
Metabolomics
STUDY_SUMMARY
This metabolomics study evaluated kidney tissue from wild-type and meprin β knockout mice after induction of diabetes with streptozotocin or treatment with sodium citrate control to understand how these factors influence the metabotype.
INSTITUTE
RTI International
DEPARTMENT
Discovery-Sciences-Technology (DST)
LABORATORY
NIH Eastern Regional Comphrehensive Metabolomics Resource Core at UNC Chapel Hill (ERCMRC)
LAST_NAME
Sumner
FIRST_NAME
Susan
ADDRESS
3040 E Cornwallis Road, Research Triangle Park, NC 27709
High Resolution orbittrap Mass Spectrometer to measure low abundance isotope enrichment in individual muscle proteins
STUDY_TYPE
isotope encrichment and comparison of mass spectrometer platforms
STUDY_SUMMARY
Stable isotope-labeled amino acids have long been used to measure the fractional synthesis rate of proteins, although the mass spectrometry platforms used for such analyses have changed throughout the years. More recently, tandem mass spectrometers such as triple quadrupoles have been accepted as the standard platform for enrichment measurement due to their sensitivity and the enhanced specificity offered by multiple reaction monitoring (MRM) experiments. The limit in the utility of such platforms for enrichment analysis occurs when measuring very low levels of enrichment from small amounts of sample, particularly proteins isolated from two-dimensional gel electrophoresis (2D-GE), where interference from contaminant ions impact the sensitivity of the measurement. We therefore applied a high resolution orbitrap mass spectrometer to the analysis of [ring-13C6]-phenylalanine enrichment in individual muscle proteins isolated with 2D-GE. Comparison of samples analyzed on both platforms revealed that the high resolution MS has significantly improved sensitivity relative to the triple quadrupole MS at very low-level enrichments due to its ability to resolve interferences in the m/z dimension.
Replication study: The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate
STUDY_SUMMARY
The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered Report describes the proposed replication plan of key experiments from “The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate” by Ward and colleagues, published in Cancer Cell in 2010 (Ward et al., 2010). The experiments that will be replicated are those reported in Figures 2, 3 and 5. Ward and colleagues demonstrate the mutations in isocitrate dehydrogenase 2 (IDH2), commonly found in acute myeloid leukemia (AML), abrogate the enzyme’s wild-type activity and confer to the mutant neomorphic activity that produces the oncometabolite 2-hydroxyglutarate (2-HG) (Figures 2 and 3). They then show that elevated levels of 2-HG are correlated with mutations in IDH1 and IDH2in AML patient samples (Figure 5). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published by eLife.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
Health Sciences Drive, Davis, California, 95616, USA
Investigating large scale metabolomics in mice serum lacking insulin receptors and IGF-1 receptors
STUDY_SUMMARY
Large scale metabolomics from control, M-IR-/-, M-IGF1R-/- , and MIGIRKO mice serum. Also compare mice on a chow diet to mice on a high fat diet (HFD).
Investigating large scale metabolomics in mice tissue lacking insulin receptors and IGF-1 receptors
STUDY_SUMMARY
Large scale metabolomics from control, M-IR-/-, M-IGF1R-/- , and MIGIRKO mice tissue. Also compare mice on a chow diet to mice on a high fat diet (HFD).
Plasma metabolomic profiling of diabetic nephropathy in the steptozotocin induced type-1 diabetes mouse model
STUDY_SUMMARY
This metabolomics study evaluated plasma from wild-type and meprin β knockout mice after induction of diabetes with streptozotocin or treatment with sodium citrate control to understand how these factors influence the metabotype.
INSTITUTE
RTI International
LAST_NAME
Sumner
FIRST_NAME
Susan
ADDRESS
3040 E. Cornwallis Road, Research Triangle Park, NC 27709
Urine metabolomic profiling of diabetic nephropathy in the steptozotocin induced type-1 diabetes mouse model.
STUDY_SUMMARY
This metabolomics study evaluated urine from wild-type and meprin β knockout mice after induction of diabetes with streptozotocin or treatment with sodium citrate control to understand how these factors influence the metabotype.
INSTITUTE
RTI International
LABORATORY
NIH Eastern Regional Comphrehensive Metabolomics Resource Core at UNC Chapel Hill (ERCMRC)
LAST_NAME
Sumner
FIRST_NAME
Susan
ADDRESS
3040 E. Cornwallis Road, Research Triangle Park, NC 27709
In this study the F8 population of 100 Recombinant Inbred Lines (RILs) obtained from a cross between Solanum lycopersicum X Solanum pimpinellifolium were intelligently allocated to two sub-populations optimized for the distribution of parental alleles using the R-procedure DesignGG (Li et al., 2009; Joosen et al., 2013); hence 50 RIL lines were used for dry seeds and 50 lines for 6h imbibed seeds
INSTITUTE
Wageningen UR
DEPARTMENT
Plant Physiology
LABORATORY
Wageningen Seed Lab, Lab
LAST_NAME
Ligterink
FIRST_NAME
Wilco
ADDRESS
Droevendaalsesteeg 1, NL-6708 PB Wageningen, The Netherlands
Large Scale C18 Profiling of the Effects of Curcumin Supplementation of Older Adults: Relation to Vascular Function
STUDY_SUMMARY
Perform large scale profiling C18 metabolite analysis related to nitric oxide biology, oxidative stress and inflammation in plasma before and after 12 weeks of oral curcumin (2000 mg/d) or placebo (double-blind, randomized) in men and women aged 45-79 years who are free from clinical cardiovascular disease.
INSTITUTE
Mayo Clinic
LAST_NAME
Seals
FIRST_NAME
Douglas
ADDRESS
Department of Integrative Physiology University of Colorado Boulder, CO 80309
Large Scale HILIC Profiling of the Effects of Curcumin Supplementation of Older Adults: Relation to Vascular Function
STUDY_SUMMARY
Perform large scale profiling HILIC metabolite analysis related to nitric oxide biology, oxidative stress and inflammation in plasma before and after 12 weeks of oral curcumin (2000 mg/d) or placebo (double-blind, randomized) in men and women aged 45-79 years who are free from clinical cardiovascular disease.
INSTITUTE
Mayo Clinic
LAST_NAME
Seals
FIRST_NAME
Douglas
ADDRESS
Department of Integrative Physiology University of Colorado Boulder, CO 80309
Exploratory research on first and second trimester urinary metabolic profiles and fetal growth restriction
STUDY_SUMMARY
From 2010 to 2012, women were recruited into The Infant Development and the Environment Study (TIDES) from obstetrical clinics affiliated with academic medical centers in four U.S. cities. Using previously collected first and second trimester urine samples from this prospective cohort of nearly 800 pregnancies, we designed a nested case control study aimed to determine whether maternal metabolic abnormalities/differences are associated with FGR. To find the patients with fetal growth restriction (FGR), we reviewed de-identified questionnaires and de-identified previously collected data, and performed a growth potential formula considering gestational age, infant gender, maternal and paternal height, and interaction of gestational age with maternal weight. Using a case:control ratio of 1:2, matched on study site, maternal age (± 2 years), parity, and infant's sex, 53 cases were matched to 106 controls for a total of 159 patients, and 318 samples (one in each ttrimester). The samples were analyses by NMR spectroscopy, using Bruker IVDr platform. Identification of FGR cases and controls: FGR cases were determined using the AUDIPOG formula for the average predicted birthweight for an infant with specific characteristics of: maternal height, age, and prenatal weight, as well as infant sex, gestational age, and birth rank. AUDIPOG formula: avg_pred_bw = 10,228066774 - 0,646727171*GA + 0,0259713417*GA² - 0,000291122*GA³ - 0,045467351*sex + 0,0606013862*rank - 0,013592585*rank² + 0,0009109473*rank³ + 0,0003976103*MA + 0,0019992269*MH + 0,0169049061*MW - 0,000171266*MW² + 5,8340462E-7*MW³ The natural logarithm of this average predicted birthweight was used with the observed birthweight to determine a z-score and percentile for each infant. If an infant fell into the 10th percentile for his or her given characteristics, then they were considered as having FGR. Otherwise they were considered in the pool of controls.
INSTITUTE
Mayo Clinic
LAST_NAME
Vuckovic
FIRST_NAME
Ivan
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Effects of the Kinase Inhibitor Sorafenib on Serum Metabolism In Vivo using Non-targeted Metabolomics Analysis tissue).
STUDY_SUMMARY
The human kinome consists of ~500 kinases, including 150 proposed as therapeutic targets. progression, cell death, differentiation, and survival. It is not surprising, then, that new tyrosine kinase inhibitors (TKIs) developed to treat cancer also exhibit cardiotoxicity, including sorafenib. We hypothesized that sorafenib cardiotoxicity is related to its deleterious effects on specific cardiac metabolic pathways given the critical role of TKs in cardiac metabolism. FVB/N mice (10/group) were challenged with sorafenib or vehicle control daily for two weeks. Echocardiographic assessment of the heart identified systolic dysfunction consistent with cardiotoxicity compared to vehicle treated controls. Cardiac, skeletal muscle, liver, and serum were flash frozen and prepped for non-targeted GC-MS metabolomics analysis. Compared to vehicle treated controls, sorafenib-treated hearts exhibited significant alterations in 11 metabolites, including markedly altered taurine/hypotaurine metabolism by pathway enrichment analysis (25-fold enrichment). These studies identify sorafenib-induced alterations in cardiac alanine and taurine/hypotaurine metabolic. Interventions to rescue or prevent sorafenib-related cardiotoxicity warrant consideration of therapies targeting the taurine/hypotaurine deficiency identified in the current study.
INSTITUTE
University of North Carolina
DEPARTMENT
McAllister heart Institute, Department of Internal medicine
LABORATORY
Multiple Centers
LAST_NAME
Willis
FIRST_NAME
Monte
ADDRESS
111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA
Effects of the Kinase Inhibitor Sorafenib on Muscle Metabolism In Vivo using Non-targeted Metabolomics Analysis tissue).
STUDY_SUMMARY
The human kinome consists of ~500 kinases, including 150 proposed as therapeutic targets. progression, cell death, differentiation, and survival. It is not surprising, then, that new tyrosine kinase inhibitors (TKIs) developed to treat cancer also exhibit cardiotoxicity, including sorafenib. We hypothesized that sorafenib cardiotoxicity is related to its deleterious effects on specific cardiac metabolic pathways given the critical role of TKs in cardiac metabolism. FVB/N mice (10/group) were challenged with sorafenib or vehicle control daily for two weeks. Echocardiographic assessment of the heart identified systolic dysfunction consistent with cardiotoxicity compared to vehicle treated controls. Cardiac, skeletal muscle, liver, and serum were flash frozen and prepped for non-targeted GC-MS metabolomics analysis. Compared to vehicle treated controls, sorafenib-treated hearts exhibited significant alterations in 11 metabolites, including markedly altered taurine/hypotaurine metabolism by pathway enrichment analysis (25-fold enrichment). These studies identify sorafenib-induced alterations in cardiac alanine and taurine/hypotaurine metabolic. Interventions to rescue or prevent sorafenib-related cardiotoxicity warrant consideration of therapies targeting the taurine/hypotaurine deficiency identified in the current study.
INSTITUTE
University of North Carolina
DEPARTMENT
McAllister heart Institute, Department of Internal medicine
LABORATORY
Multiple Centers
LAST_NAME
Willis
FIRST_NAME
Monte
ADDRESS
111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA
Effects of the Kinase Inhibitor Sorafenib on Heart Metabolism In Vivo using Non-targeted Metabolomics Analysis tissue).
STUDY_SUMMARY
The human kinome consists of ~500 kinases, including 150 proposed as therapeutic targets. progression, cell death, differentiation, and survival. It is not surprising, then, that new tyrosine kinase inhibitors (TKIs) developed to treat cancer also exhibit cardiotoxicity, including sorafenib. We hypothesized that sorafenib cardiotoxicity is related to its deleterious effects on specific cardiac metabolic pathways given the critical role of TKs in cardiac metabolism. FVB/N mice (10/group) were challenged with sorafenib or vehicle control daily for two weeks. Echocardiographic assessment of the heart identified systolic dysfunction consistent with cardiotoxicity compared to vehicle treated controls. Cardiac, skeletal muscle, liver, and serum were flash frozen and prepped for non-targeted GC-MS metabolomics analysis. Compared to vehicle treated controls, sorafenib-treated hearts exhibited significant alterations in 11 metabolites, including markedly altered taurine/hypotaurine metabolism by pathway enrichment analysis (25-fold enrichment). These studies identify sorafenib-induced alterations in cardiac alanine and taurine/hypotaurine metabolic. Interventions to rescue or prevent sorafenib-related cardiotoxicity warrant consideration of therapies targeting the taurine/hypotaurine deficiency identified in the current study.
INSTITUTE
University of North Carolina
DEPARTMENT
McAllister heart Institute, Department of Internal medicine
LABORATORY
Multiple Centers
LAST_NAME
Willis
FIRST_NAME
Monte
ADDRESS
111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA
Effects of the Kinase Inhibitor Sorafenib on Liver Metabolism In Vivo using Non-targeted Metabolomics Analysis tissue).
STUDY_SUMMARY
The human kinome consists of ~500 kinases, including 150 proposed as therapeutic targets. progression, cell death, differentiation, and survival. It is not surprising, then, that new tyrosine kinase inhibitors (TKIs) developed to treat cancer also exhibit cardiotoxicity, including sorafenib. We hypothesized that sorafenib cardiotoxicity is related to its deleterious effects on specific cardiac metabolic pathways given the critical role of TKs in cardiac metabolism. FVB/N mice (10/group) were challenged with sorafenib or vehicle control daily for two weeks. Echocardiographic assessment of the heart identified systolic dysfunction consistent with cardiotoxicity compared to vehicle treated controls. Cardiac, skeletal muscle, liver, and serum were flash frozen and prepped for non-targeted GC-MS metabolomics analysis. Compared to vehicle treated controls, sorafenib-treated hearts exhibited significant alterations in 11 metabolites, including markedly altered taurine/hypotaurine metabolism by pathway enrichment analysis (25-fold enrichment). These studies identify sorafenib-induced alterations in cardiac alanine and taurine/hypotaurine metabolic. Interventions to rescue or prevent sorafenib-related cardiotoxicity warrant consideration of therapies targeting the taurine/hypotaurine deficiency identified in the current study.
INSTITUTE
University of North Carolina
DEPARTMENT
McAllister heart Institute, Department of Internal medicine
LABORATORY
Multiple Centers
LAST_NAME
Willis
FIRST_NAME
Monte
ADDRESS
111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA
AH and TM samples were obtained from young-normotensive DBA/2J (3 and 7.5 months) and old-hypertensive DBA/2J mice (8-8.5, 10 and 12 month). Lipids were extracted using modified Bligh and Dyer method and subjected to mass spectrometric identification using appropriate class-specific lipid standards and ratiometric quantification. Corresponding aqueous phase (of extraction) protein concentrations were measured using Bradford method.
INSTITUTE
University of Miami
LAST_NAME
Bhattacharya
FIRST_NAME
Sanjoy
ADDRESS
McKnight Vision Research Building, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 1638 NW 10th Avenue, Room 706A, Miami, Florida 33136
Metabolomics of Exhaled Breath Condensate in Decompensated Heart Failure
STUDY_SUMMARY
The aim of the study was to test weather characteristic differences or changes in metabolic profile exist between exhaled breath condensate (EBC) and saliva of healthy individuals and heart failure patients. EBC NMR profiling was performed.
Metabolomics of Saliva in Decompensated Heart Failure
STUDY_SUMMARY
The aim of the study was to test weather characteristic differences or changes in metabolic profile exist between exhaled breath condensate (EBC) and saliva of healthy individuals and heart failure patients. Salival NMR profiling was performed.
Multi-site, cross-sectional study, including subjects with Age-related Macular Degeneration (early, intermediate and late disease) and a control group of subjects without any macular diseases. Plasma metabolomic profiles were assessed using Nuclear Magnetic Resonance Spectroscopy (NMR). Multivariate statistics were performed to compare metabolomic profiles of AMD patients vs controls.
INSTITUTE
University of Aveiro
DEPARTMENT
Department of Chemistry and CICECO_Aveiro Institute of Materials
LABORATORY
University of Aveiro
LAST_NAME
Gil
FIRST_NAME
Ana
ADDRESS
Campus de Santiago, Aveiro, Aveiro, 3810-193, Portugal
PIXiE: An Algorithm for Automated Ion Mobility Arrival Time Extraction and Collision Cross Section Calculation using Global Data Association
STUDY_SUMMARY
Motivation: Drift tube ion mobility spectrometry coupled with mass spectrometry (DTIMS-MS) is increasingly implemented in high throughput omics workflows, and new informatics approaches are necessary for processing the associated data. To automatically extract arrival times for molecules measured by DTIMS at multiple electric fields and compute their associated collisional cross sections (CCS), we created the PNNL Ion Mobility Cross Section Extractor (PIXiE). The primary application presented for this algorithm is the extraction of that can then be used to create a reference library of CCS valuesinformation necessary to create a reference library containing accurate masses, DTIMS arrival times and CCSs for use in high throughput omics analyses. Results: We demonstrate the utility of this approach by automatically extracting arrival times and calculating the associated CCSs for a set of endogenous metabolites and xenobiotics. The PIXiE-generated CCS values were within error of those calculated using commercially available instrument vendor software.
Smoking induced methylation plays a critical role in the accumulation of methylated metabolites, DNA adducts damage and altered metabolism in BCa. These deregulated metabolites can be detected non-invasively and can be used as causal biomarkers that can predict the risk of developing BCa in smokers
A structural examination and collision cross section database of over 500 metabolities and xenobiotics using drift tube ion mobility
STUDY_TYPE
Library compilation of metabolomic standards
STUDY_SUMMARY
Standards of metabolomic pathways and external secondary metabolites and xenobiotics were analysed with Agilent 6560 Ion mobility QTOF MS platform to build a comprehensive library of Collision Cross Section values. All measurements were performed in triplicate in both positive and negative polarities with nitrogen gas and at seven different electric fields, so that values could be directly measured and random standard deviations (RSD) assessed for each molecule.
INSTITUTE
Pacific Northwest National Laboratory
DEPARTMENT
Integrative Omics
LABORATORY
Pacific Northwest National Laboratory
LAST_NAME
Baker
FIRST_NAME
Erin
ADDRESS
Pacific Northwest National Laboratory, 902 Battelle Boulevard, Richland, WA
Non-targeted Metabolomics Analysis of Golden Retriever Muscular Dystrophy-Affected Muscles Reveals Alterations in Arginine and Proline Metabolism, and Elevations in Glutamic and Oleic Acid In Vivo
STUDY_SUMMARY
Like Duchenne muscular dystrophy (DMD), the Golden Retriever Muscular Dystrophy (GRMD) dog model of DMD exhibits is characterized by muscle necrosis, progressive paralysis, and pseudohypertrophy in specific skeletal muscles. This severe GRMD phenotype included atrophy of the biceps femoris (BF) and compared to unaffected normal dogs, while the long digital extensor (LDE) of the pelvic limb, serving as a hip flex and stifle extensor, is unaffected. A recent microarray analysis of GRMD identified alterations in genes associated with lipid metabolism and energy production. We, therefore, undertook a non-targeted metabolomics analysis of the GRMD BF (affected) and LDE (unaffected) using GC-MS to identify underlying metabolic defects specific for affected GRMD skeletal muscle. Of the 134 metabolites identified in BF, eight were significantly altered in GRMD BF compared to control BF (Glutamic Acid (2.48 fold vs. controls); Oleic Acid (1.76 fold vs. controls); Proline (1.73 fold vs. controls); Myoinositol-2- Phosphate (0.44 fold vs. controls); Fumaric Acid (0.40 fold vs. controls); Carnosine (0.40 fold vs. controls); Lactamide (0.33 fold vs. controls); and Stearamide (0.23 fold vs. controls). Pathway analysis of the T-test significant metabolites identified BF muscle metabolites significantly enriched for Arginine and proline metabolism (p=5.8E-4, FDR=0.04) and Alanine, aspartate, and glutamate metabolism (p=1.3E-3, FDR=0.05). The GRMD LDE previously reported to be unaffected, in contrast, had only one significantly altered metabolite (3-Phosphoglyceric Acid (0.35 Fold vs. controls)).The identification of elevated BF Oleic acid (a long-chain fatty acid) is consistent with recent microarray studies identifying altered lipid metabolism genes, while alterations in Arginine and Proline metabolism are consistent with recent studies identifying elevated L-arginine in DMD patient sera as a biomarker of disease (alterations in DMD or GRMD muscle itself have not previously been reported).Together, these studies demonstrate muscle-specific alterations in GRMD-affected muscle, which illustrate previously unidentified metabolic changes.
INSTITUTE
University of North Carolina
DEPARTMENT
McAllister heart Institute, Department of Internal medicine, Department of Pathology & Laboratory, Department of Pharmacology
LABORATORY
Multiple Centers
LAST_NAME
Willis
FIRST_NAME
Monte
ADDRESS
111 Mason Farm Road, MBRB 2336, Chapel Hill, North Carolina, 27599-7126, USA
EMAIL
monte_willis@med.unc.edu
PHONE
(984) 999-5431
STUDY_COMMENTS
Skeletal Muscle (Biceps femoris (BF), long digital extensor(LDE))
Non targeted metabolomic analysis of mouse and human bronchoalveolar lavage fluid, Lipid(+) experiment (part III)
STUDY_TYPE
Comprehensive profile
STUDY_SUMMARY
Mouse BALF was collected from C57BL/6 mice (n = 10). Five mice were exposed to ambient air for one day (air control) and five mice were exposed to CS for nine months (smoking). Human BALF was collected from subjects from the COPDGene cohort (n = 5). COPD diagnosis was based on the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC). Subjects were 45-70 years old, BMI 27-45, weight 76-125kg, and were categorized as follows: 1 male former smoker without COPD (FEV1/FVC = 0.82), 2 male current smokers without COPD (FEV1/FVC = 0.91 and 0.79), 1 female current smoker with moderate COPD (FEV1/FVC = 0.51), and 1 male current smoker with moderate COPD (FEV1/FVC = 0.64)
TCA Cycle Metabolites of Dietary Salt Effects on Blood Pressure in Human Urine from 20 Participants of the DASH2 Clinical Trial
STUDY_SUMMARY
The objective of the study is to identify changes of urinary metabolite profiles associated with different responses to blood pressure to salt. Subjects are derived from The Dietary approaches to stop hypertension (DASH) diet, Sodium Intake and Blood Pressure Trial (Sacks FM et al PMID: 11136953,N Engl J Med. 2001).We choose two groups subjects who meet the following conditions(the two groups are separately named A and B). We chose subjects on the Control diet .These subjects meet the blood pressure criteria described below:Group A subjects conditions: 1) On Control diet. 2) Normotensive subjects: systolic blood pressure from the low sodium visit is less than 140 and the diastolic blood pressure from low sodium visit is less than 90; 3) For group A: Either the systolic blood pressure from the high sodium visit was greater than 10 mmHg higher than the systolic blood pressure from the low sodium visit, or the diastolic blood pressure from the high sodium visit was greater than 10 mmHg higher than the diastolic blood pressure from the low sodium visit; 3) For group B: The systolic blood pressure from the high sodium visit is within 5 mmHg (i.e. +/- 5) from the systolic blood pressure from the low sodium visit, and the diastolic blood pressure from the high sodium visit is within 5 mmHg from the diastolic blood pressure from the low sodium visit. Use gas chromatography/mass spectrometry (GC/MS) analysis, and liquid chromatography/mass spectrometry (LC/MS)analysis to find the differences of metabolic profiles between the high sodium level and the low sodium level, and compare the metabolic profiles of A with the metabolic profiles of B at the low and high sodium level. Note, this was used as a pilot, the rest of the samples are in another uploaded study.
INSTITUTE
Mayo Clinic
LAST_NAME
Liang
FIRST_NAME
Mingyu
ADDRESS
Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226
Amino Acd Metabolites of Dietary Salt Effects on Blood Pressure in Human Urine from 20 Participants of the DASH2 Clinical Trial (part II)
STUDY_SUMMARY
The objective of the study is to identify changes of urinary metabolite profiles associated with different responses to blood pressure to salt. Subjects are derived from The Dietary approaches to stop hypertension (DASH) diet, Sodium Intake and Blood Pressure Trial (Sacks FM et al PMID: 11136953,N Engl J Med. 2001).We choose two groups subjects who meet the following conditions(the two groups are separately named A and B). We chose subjects on the Control diet .These subjects meet the blood pressure criteria described below:Group A subjects conditions: 1) On Control diet. 2) Normotensive subjects: systolic blood pressure from the low sodium visit is less than 140 and the diastolic blood pressure from low sodium visit is less than 90; 3) For group A: Either the systolic blood pressure from the high sodium visit was greater than 10 mmHg higher than the systolic blood pressure from the low sodium visit, or the diastolic blood pressure from the high sodium visit was greater than 10 mmHg higher than the diastolic blood pressure from the low sodium visit; 3) For group B: The systolic blood pressure from the high sodium visit is within 5 mmHg (i.e. +/- 5) from the systolic blood pressure from the low sodium visit, and the diastolic blood pressure from the high sodium visit is within 5 mmHg from the diastolic blood pressure from the low sodium visit. Use gas chromatography/mass spectrometry (GC/MS) analysis, and liquid chromatography/mass spectrometry (LC/MS)analysis to find the differences of metabolic profiles between the high sodium level and the low sodium level, and compare the metabolic profiles of A with the metabolic profiles of B at the low and high sodium level. Note, this was used as a pilot, the rest of the samples are in another uploaded study.
INSTITUTE
Mayo Clinic
LAST_NAME
Liang
FIRST_NAME
Mingyu
ADDRESS
Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226
Neuromodulator Metabolites of Dietary Salt Effects on Blood Pressure in Human Urine from 20 Participants of the DASH2 Clinical Trial (part III)
STUDY_SUMMARY
The objective of the study is to identify changes of urinary metabolite profiles associated with different responses to blood pressure to salt. Subjects are derived from The Dietary approaches to stop hypertension (DASH) diet, Sodium Intake and Blood Pressure Trial (Sacks FM et al PMID: 11136953,N Engl J Med. 2001).We choose two groups subjects who meet the following conditions(the two groups are separately named A and B). We chose subjects on the Control diet .These subjects meet the blood pressure criteria described below:Group A subjects conditions: 1) On Control diet. 2) Normotensive subjects: systolic blood pressure from the low sodium visit is less than 140 and the diastolic blood pressure from low sodium visit is less than 90; 3) For group A: Either the systolic blood pressure from the high sodium visit was greater than 10 mmHg higher than the systolic blood pressure from the low sodium visit, or the diastolic blood pressure from the high sodium visit was greater than 10 mmHg higher than the diastolic blood pressure from the low sodium visit; 3) For group B: The systolic blood pressure from the high sodium visit is within 5 mmHg (i.e. +/- 5) from the systolic blood pressure from the low sodium visit, and the diastolic blood pressure from the high sodium visit is within 5 mmHg from the diastolic blood pressure from the low sodium visit. Use gas chromatography/mass spectrometry (GC/MS) analysis, and liquid chromatography/mass spectrometry (LC/MS)analysis to find the differences of metabolic profiles between the high sodium level and the low sodium level, and compare the metabolic profiles of A with the metabolic profiles of B at the low and high sodium level. Note, this was used as a pilot, the rest of the samples are in another uploaded study.
INSTITUTE
Mayo Clinic
LAST_NAME
Liang
FIRST_NAME
Mingyu
ADDRESS
Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226
TCA Cycle Metabolites of Dietary Salt Effects on Blood Pressure in Rat Urine (part IV)
STUDY_SUMMARY
We propose to analyze kidney tissue extract and urine samples from SS and SS.Fh1+ transgenic rats in addition to the analysis of urine samples from the DASH2 trial. The analysis of the rat samples will be highly valuable for several reasons. First, it will to take the findings in human subjects back to animal models and prepare us for further mechanistic studies. We hypothesize at least some of the effects of dietary salt intake on metabolite profiles in human will be recapitulated or altered in the SS rat. If this is confirmed, we will have a highly informative animal model ready for mechanistic studies in which we can investigate the functional contribution of specific metabolites to hypertension and the mechanisms involved. Second, the rat study will allow us to take advantage of a new and unique transgenic SS.Fh1+ model that we recently developed that overexpresses fumarase (Fh1) on the genetic background of the SS rat. Fumarase is a TCA cycle enzyme previously implicated in salt-induced hypertension in SS rats.
INSTITUTE
Mayo Clinic
LAST_NAME
Liang
FIRST_NAME
Mingyu
ADDRESS
Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226
Amino Acid Metabolites of Dietary Salt Effects on Blood Pressure in Rat Urine (part V)
STUDY_SUMMARY
We propose to analyze kidney tissue extract and urine samples from SS and SS.Fh1+ transgenic rats in addition to the analysis of urine samples from the DASH2 trial. The analysis of the rat samples will be highly valuable for several reasons. First, it will to take the findings in human subjects back to animal models and prepare us for further mechanistic studies. We hypothesize at least some of the effects of dietary salt intake on metabolite profiles in human will be recapitulated or altered in the SS rat. If this is confirmed, we will have a highly informative animal model ready for mechanistic studies in which we can investigate the functional contribution of specific metabolites to hypertension and the mechanisms involved. Second, the rat study will allow us to take advantage of a new and unique transgenic SS.Fh1+ model that we recently developed that overexpresses fumarase (Fh1) on the genetic background of the SS rat. Fumarase is a TCA cycle enzyme previously implicated in salt-induced hypertension in SS rats.
INSTITUTE
Mayo Clinic
LAST_NAME
Liang
FIRST_NAME
Mingyu
ADDRESS
Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226
Neuromodulator Metabolites of Dietary Salt Effects on Blood Pressure in Rat Urine (part VI)
STUDY_SUMMARY
We propose to analyze kidney tissue extract and urine samples from SS and SS.Fh1+ transgenic rats in addition to the analysis of urine samples from the DASH2 trial. The analysis of the rat samples will be highly valuable for several reasons. First, it will to take the findings in human subjects back to animal models and prepare us for further mechanistic studies. We hypothesize at least some of the effects of dietary salt intake on metabolite profiles in human will be recapitulated or altered in the SS rat. If this is confirmed, we will have a highly informative animal model ready for mechanistic studies in which we can investigate the functional contribution of specific metabolites to hypertension and the mechanisms involved. Second, the rat study will allow us to take advantage of a new and unique transgenic SS.Fh1+ model that we recently developed that overexpresses fumarase (Fh1) on the genetic background of the SS rat. Fumarase is a TCA cycle enzyme previously implicated in salt-induced hypertension in SS rats.
INSTITUTE
Mayo Clinic
LAST_NAME
Liang
FIRST_NAME
Mingyu
ADDRESS
Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226
TCA Cycle Metabolites of Dietary Salt Effects on Blood Pressure in Human Urine from DASH2 Clinical Trial (part VII)
STUDY_SUMMARY
The objective of the study is to identify changes of urinary metabolite profiles associated with different responses to blood pressure to salt. Subjects are derived from The Dietary approaches to stop hypertension (DASH) diet, Sodium Intake and Blood Pressure Trial (Sacks FM et al PMID: 11136953,N Engl J Med. 2001).We choose two groups subjects who meet the following conditions(the two groups are separately named A and B). We chose subjects on the Control diet .These subjects meet the blood pressure criteria described below:Group A subjects conditions: 1) On Control diet. 2) Normotensive subjects: systolic blood pressure from the low sodium visit is less than 140 and the diastolic blood pressure from low sodium visit is less than 90; 3) For group A: Either the systolic blood pressure from the high sodium visit was greater than 10 mmHg higher than the systolic blood pressure from the low sodium visit, or the diastolic blood pressure from the high sodium visit was greater than 10 mmHg higher than the diastolic blood pressure from the low sodium visit; 3) For group B: The systolic blood pressure from the high sodium visit is within 5 mmHg (i.e. +/- 5) from the systolic blood pressure from the low sodium visit, and the diastolic blood pressure from the high sodium visit is within 5 mmHg from the diastolic blood pressure from the low sodium visit. Use gas chromatography/mass spectrometry (GC/MS) analysis, and liquid chromatography/mass spectrometry (LC/MS)analysis to find the differences of metabolic profiles between the high sodium level and the low sodium level, and compare the metabolic profiles of A with the metabolic profiles of B at the low and high sodium level.
INSTITUTE
Mayo Clinic
LAST_NAME
Liang
FIRST_NAME
Mingyu
ADDRESS
Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226
Amino Acid Metabolites of Dietary Salt Effects on Blood Pressure in Human Urine from DASH2 Clinical Trial (part VIII)
STUDY_SUMMARY
The objective of the study is to identify changes of urinary metabolite profiles associated with different responses to blood pressure to salt. Subjects are derived from The Dietary approaches to stop hypertension (DASH) diet, Sodium Intake and Blood Pressure Trial (Sacks FM et al PMID: 11136953,N Engl J Med. 2001).We choose two groups subjects who meet the following conditions(the two groups are separately named A and B). We chose subjects on the Control diet .These subjects meet the blood pressure criteria described below:Group A subjects conditions: 1) On Control diet. 2) Normotensive subjects: systolic blood pressure from the low sodium visit is less than 140 and the diastolic blood pressure from low sodium visit is less than 90; 3) For group A: Either the systolic blood pressure from the high sodium visit was greater than 10 mmHg higher than the systolic blood pressure from the low sodium visit, or the diastolic blood pressure from the high sodium visit was greater than 10 mmHg higher than the diastolic blood pressure from the low sodium visit; 3) For group B: The systolic blood pressure from the high sodium visit is within 5 mmHg (i.e. +/- 5) from the systolic blood pressure from the low sodium visit, and the diastolic blood pressure from the high sodium visit is within 5 mmHg from the diastolic blood pressure from the low sodium visit. Use gas chromatography/mass spectrometry (GC/MS) analysis, and liquid chromatography/mass spectrometry (LC/MS)analysis to find the differences of metabolic profiles between the high sodium level and the low sodium level, and compare the metabolic profiles of A with the metabolic profiles of B at the low and high sodium level.
INSTITUTE
Mayo Clinic
LAST_NAME
Liang
FIRST_NAME
Mingyu
ADDRESS
Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226
Neuromodulator Metabolites of Dietary Salt Effects on Blood Pressure in Human Urine from DASH2 Clinical Trial (part IX)
STUDY_SUMMARY
The objective of the study is to identify changes of urinary metabolite profiles associated with different responses to blood pressure to salt. Subjects are derived from The Dietary approaches to stop hypertension (DASH) diet, Sodium Intake and Blood Pressure Trial (Sacks FM et al PMID: 11136953,N Engl J Med. 2001).We choose two groups subjects who meet the following conditions(the two groups are separately named A and B). We chose subjects on the Control diet .These subjects meet the blood pressure criteria described below:Group A subjects conditions: 1) On Control diet. 2) Normotensive subjects: systolic blood pressure from the low sodium visit is less than 140 and the diastolic blood pressure from low sodium visit is less than 90; 3) For group A: Either the systolic blood pressure from the high sodium visit was greater than 10 mmHg higher than the systolic blood pressure from the low sodium visit, or the diastolic blood pressure from the high sodium visit was greater than 10 mmHg higher than the diastolic blood pressure from the low sodium visit; 3) For group B: The systolic blood pressure from the high sodium visit is within 5 mmHg (i.e. +/- 5) from the systolic blood pressure from the low sodium visit, and the diastolic blood pressure from the high sodium visit is within 5 mmHg from the diastolic blood pressure from the low sodium visit. Use gas chromatography/mass spectrometry (GC/MS) analysis, and liquid chromatography/mass spectrometry (LC/MS)analysis to find the differences of metabolic profiles between the high sodium level and the low sodium level, and compare the metabolic profiles of A with the metabolic profiles of B at the low and high sodium level.
INSTITUTE
Mayo Clinic
LAST_NAME
Liang
FIRST_NAME
Mingyu
ADDRESS
Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226
TCA Cycle Metabolites of Dietary Salt Effects on Blood Pressure in Rat Urine and Kidney Tissue (part X)
STUDY_SUMMARY
We propose to analyze kidney tissue extract and urine samples from SS and SS.Fh1+ transgenic rats in addition to the analysis of urine samples from the DASH2 trial. The analysis of the rat samples will be highly valuable for several reasons. First, it will to take the findings in human subjects back to animal models and prepare us for further mechanistic studies. We hypothesize at least some of the effects of dietary salt intake on metabolite profiles in human will be recapitulated or altered in the SS rat. If this is confirmed, we will have a highly informative animal model ready for mechanistic studies in which we can investigate the functional contribution of specific metabolites to hypertension and the mechanisms involved. Second, the rat study will allow us to take advantage of a new and unique transgenic SS.Fh1+ model that we recently developed that overexpresses fumarase (Fh1) on the genetic background of the SS rat. Fumarase is a TCA cycle enzyme previously implicated in salt-induced hypertension in SS rats.
INSTITUTE
Mayo Clinic
LAST_NAME
Liang
FIRST_NAME
Mingyu
ADDRESS
Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226
Amino Acid Metabolites of Dietary Salt Effects on Blood Pressure in Rat Urine and Kidney Tissue (part I)
STUDY_SUMMARY
We propose to analyze kidney tissue extract and urine samples from SS and SS.Fh1+ transgenic rats in addition to the analysis of urine samples from the DASH2 trial. The analysis of the rat samples will be highly valuable for several reasons. First, it will to take the findings in human subjects back to animal models and prepare us for further mechanistic studies. We hypothesize at least some of the effects of dietary salt intake on metabolite profiles in human will be recapitulated or altered in the SS rat. If this is confirmed, we will have a highly informative animal model ready for mechanistic studies in which we can investigate the functional contribution of specific metabolites to hypertension and the mechanisms involved. Second, the rat study will allow us to take advantage of a new and unique transgenic SS.Fh1+ model that we recently developed that overexpresses fumarase (Fh1) on the genetic background of the SS rat. Fumarase is a TCA cycle enzyme previously implicated in salt-induced hypertension in SS rats.
INSTITUTE
Mayo Clinic
LAST_NAME
Liang
FIRST_NAME
Mingyu
ADDRESS
Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226
Neuromodulator Metabolites of Dietary Salt Effects on Blood Pressure in Rat Urine and Kidney Tissue (part XII)
STUDY_SUMMARY
We propose to analyze kidney tissue extract and urine samples from SS and SS.Fh1+ transgenic rats in addition to the analysis of urine samples from the DASH2 trial. The analysis of the rat samples will be highly valuable for several reasons. First, it will to take the findings in human subjects back to animal models and prepare us for further mechanistic studies. We hypothesize at least some of the effects of dietary salt intake on metabolite profiles in human will be recapitulated or altered in the SS rat. If this is confirmed, we will have a highly informative animal model ready for mechanistic studies in which we can investigate the functional contribution of specific metabolites to hypertension and the mechanisms involved. Second, the rat study will allow us to take advantage of a new and unique transgenic SS.Fh1+ model that we recently developed that overexpresses fumarase (Fh1) on the genetic background of the SS rat. Fumarase is a TCA cycle enzyme previously implicated in salt-induced hypertension in SS rats.
INSTITUTE
Mayo Clinic
LAST_NAME
Liang
FIRST_NAME
Mingyu
ADDRESS
Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226
Targeted NEFA in American Indian Adolescents (part I)
STUDY_SUMMARY
The goal of this study is to determine the effect of physical activity on the blood concentrations of several compounds that are proposed to be markers of diabetic risk. We will compare results from normal weight and obese American Indian adolescents, with high or low habitual physical activity. We will also compare the same blood markers in the obese group before and after 4 months of exercise to measure the benefit of the program.
INSTITUTE
Mayo Clinic
LAST_NAME
Short
FIRST_NAME
Kevin
ADDRESS
University of Oklahoma Health Sciences Center 1200 Children’s Ave, Suite 4500 Oklahoma City, OK 73104
Targeted Amino Acids in American Indian Adolescents (part II)
STUDY_SUMMARY
The goal of this study is to determine the effect of physical activity on the blood concentrations of several compounds that are proposed to be markers of diabetic risk. We will compare results from normal weight and obese American Indian adolescents, with high or low habitual physical activity. We will also compare the same blood markers in the obese group before and after 4 months of exercise to measure the benefit of the program.
INSTITUTE
Mayo Clinic
LAST_NAME
Short
FIRST_NAME
Kevin
ADDRESS
University of Oklahoma Health Sciences Center 1200 Children’s Ave, Suite 4500 Oklahoma City, OK 73104
Effects of Exercise on Dystrophic Mouse Muscle Amino Acids (part II)
STUDY_SUMMARY
We will use male C57BL10, mdx, and nNOS-/- mice (n = 10 each group) to characterize the skeletal and cardiac muscle metabolomes. Half of the mice in each group will remain sedentary while the other half will be subjected to a single bout of treadmill exercise to exhaustion. Mice will be euthanized immediately postexercise and blood, hearts, and hindlimb muscles will be harvested and frozen as detailed in the General Methods. The heart and gastrocnemius, soleus, and quadriceps muscles of one hindlimb will be sent to the Mayo Clinic Metabolomics Resource Core. The heart and quadriceps muscle will be used for untargeted metabolomics profiling (LC/MS) while the gastrocnemius and soleus muscles will be used for targeted analyses of amino acids plus amino metabolites, non-esterified fatty acids, and citric acid cycle intermediates.
INSTITUTE
Mayo Clinic
LAST_NAME
Thomas
FIRST_NAME
Gail
ADDRESS
Penn State Hershey Heart and Vascular Institute Penn State College of Medicine 500 University Drive, MC H047 Hershey, PA 17033
Effects of Exercise on Dystrophic Mouse Muscle TCA Cycle (part II)
STUDY_SUMMARY
We will use male C57BL10, mdx, and nNOS-/- mice (n = 10 each group) to characterize the skeletal and cardiac muscle metabolomes. Half of the mice in each group will remain sedentary while the other half will be subjected to a single bout of treadmill exercise to exhaustion. Mice will be euthanized immediately postexercise and blood, hearts, and hindlimb muscles will be harvested and frozen as detailed in the General Methods. The heart and gastrocnemius, soleus, and quadriceps muscles of one hindlimb will be sent to the Mayo Clinic Metabolomics Resource Core. The heart and quadriceps muscle will be used for untargeted metabolomics profiling (LC/MS) while the gastrocnemius and soleus muscles will be used for targeted analyses of amino acids plus amino metabolites, non-esterified fatty acids, and citric acid cycle intermediates.
INSTITUTE
Mayo Clinic
LAST_NAME
Thomas
FIRST_NAME
Gail
ADDRESS
Penn State Hershey Heart and Vascular Institute Penn State College of Medicine 500 University Drive, MC H047 Hershey, PA 17033
Effects of Exercise on Dystrophic Mouse Muscle Non-Esterified Fatty Acids (part III)
STUDY_SUMMARY
We will use male C57BL10, mdx, and nNOS-/- mice (n = 10 each group) to characterize the skeletal and cardiac muscle metabolomes. Half of the mice in each group will remain sedentary while the other half will be subjected to a single bout of treadmill exercise to exhaustion. Mice will be euthanized immediately postexercise and blood, hearts, and hindlimb muscles will be harvested and frozen as detailed in the General Methods. The heart and gastrocnemius, soleus, and quadriceps muscles of one hindlimb will be sent to the Mayo Clinic Metabolomics Resource Core. The heart and quadriceps muscle will be used for untargeted metabolomics profiling (LC/MS) while the gastrocnemius and soleus muscles will be used for targeted analyses of amino acids plus amino metabolites, non-esterified fatty acids, and citric acid cycle intermediates.
INSTITUTE
Mayo Clinic
LAST_NAME
Thomas
FIRST_NAME
Gail
ADDRESS
Penn State Hershey Heart and Vascular Institute Penn State College of Medicine 500 University Drive, MC H047 Hershey, PA 17033
Effects of NO Donor Therapy on the Dystrophic Mouse Muscle Amino Acids (part IV)
STUDY_SUMMARY
For this aim, we will only use male mdx mice. We will study three groups treated for 7 days with vehicle, naproxcinod (i.e., NO-naproxen), or naproxen (n = 10 each group). Two hours after the final treatment, half the mice in each group will be run to exhaustion on a treadmill. The heart and gastrocnemius, soleus, and quadriceps muscles of one hindlimb will be sent to the Mayo Clinic Metabolomics Resource Core. The heart and quadriceps muscle will be used for untargeted metabolomics profiling (LC/MS) while the gastrocnemius and soleus muscles will be used for targeted analyses of amino acids plus amino metabolites, non-esterified fatty acids, and citric acid cycle intermediates.
INSTITUTE
Mayo Clinic
LAST_NAME
Thomas
FIRST_NAME
Gail
ADDRESS
Penn State Hershey Heart and Vascular Institute Penn State College of Medicine 500 University Drive, MC H047 Hershey, PA 17033
Effects of NO Donor Therapy on the Dystrophic Mouse Muscle Non-Esterified Fatty Acids (part V)
STUDY_SUMMARY
For this aim, we will only use male mdx mice. We will study three groups treated for 7 days with vehicle, naproxcinod (i.e., NO-naproxen), or naproxen (n = 10 each group). Two hours after the final treatment, half the mice in each group will be run to exhaustion on a treadmill. The heart and gastrocnemius, soleus, and quadriceps muscles of one hindlimb will be sent to the Mayo Clinic Metabolomics Resource Core. The heart and quadriceps muscle will be used for untargeted metabolomics profiling (LC/MS) while the gastrocnemius and soleus muscles will be used for targeted analyses of amino acids plus amino metabolites, non-esterified fatty acids, and citric acid cycle intermediates.
INSTITUTE
Mayo Clinic
LAST_NAME
Thomas
FIRST_NAME
Gail
ADDRESS
Penn State Hershey Heart and Vascular Institute Penn State College of Medicine 500 University Drive, MC H047 Hershey, PA 17033
Effects of NO Donor Therapy on the Dystrophic Mouse Muscle TCA Cycle (part VI)
STUDY_SUMMARY
For this aim, we will only use male mdx mice. We will study three groups treated for 7 days with vehicle, naproxcinod (i.e., NO-naproxen), or naproxen (n = 10 each group). Two hours after the final treatment, half the mice in each group will be run to exhaustion on a treadmill. The heart and gastrocnemius, soleus, and quadriceps muscles of one hindlimb will be sent to the Mayo Clinic Metabolomics Resource Core. The heart and quadriceps muscle will be used for untargeted metabolomics profiling (LC/MS) while the gastrocnemius and soleus muscles will be used for targeted analyses of amino acids plus amino metabolites, non-esterified fatty acids, and citric acid cycle intermediates.
INSTITUTE
Mayo Clinic
LAST_NAME
Thomas
FIRST_NAME
Gail
ADDRESS
Penn State Hershey Heart and Vascular Institute Penn State College of Medicine 500 University Drive, MC H047 Hershey, PA 17033
Changes in metabolites and lipid mediators associated with supervised exercise training for peripheral
STUDY_TYPE
Timecourse
STUDY_SUMMARY
Peripheral artery disease (PAD) is a leading cause of cardiovascular related morbidity and mortality, affecting over 8.5 million men and women in the United States and greater than 200 million individuals worldwide. The mainstay of treatment to improve lower limb symptoms is supervised walking therapy, which does not affect plaque morphology or alter conduit artery blood flow, but rather ameliorates endothelial dysfunction, enhances skeletal muscle metabolism and mitochondrial function, and suppresses inflammatory activation. In this pilot feasibility project we will employ metabolic and lipidomic techniques to measure the effects of supervised exercise therapy on primary metabolism, complex lipids, and lipid mediators, and correlate these effects with individual, subject-level measures of the response to exercise therapy among subjects with PAD. The overarching theme of this work is to identify metabolites, complex lipids, and lipid mediators that are associated with the inter-individual variability in the response of subjects with PAD to supervised exercise therapy. This knowledge will significantly enhance our understanding of the pathophysiology of lower extremity symptoms in PAD, as well as the manner in which supervised exercise therapy improves walking intolerance. It will identify novel therapeutic targets and pathways for pharmacologic manipulation in the treatment of PAD. Aside from having the potential to generate multiple high-impact publications, it will serve as the basis for a planned NIH R01 submission by the PI at the conclusion of the award period.
INSTITUTE
USDA
DEPARTMENT
Obesity and metabolism research unit
LAST_NAME
Newman
FIRST_NAME
John
ADDRESS
430 West Health Sciences Dr. Davis, Ca, 95616
EMAIL
john.newman@ars.usda.gov
PHONE
(530) 752-1009
STUDY_COMMENTS
Fatty acids measured but not against a calibration curve. Therefore values are expressed as a relative abundance of the entire samples set such that the sum of all subjects eguals 100%.
Evaluation of plasma samples from the CHOICE clinical weight loss study in which obese post menopausal breast cancer survivors lost >15% initial body weight following either a low carbohydrate or a low fat dietary pattern. These samples will be interrogated for changes in metabolic intermediates and lipid metabolites that may be indicative of changes in prognosis for long term survival following treatment for breast cancer. Samples will be subjected to LCMS and shotgun lipidomics. In parallel, plasma and mammary gland fat pad from an obese rat model for breast cancer in which rats were subjected to a parallel level of weight loss will also be interrogated using the same procedures in an effort to inform the interpretation of the clinical data.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
These are fasted plasma samples collected from bipolar and control subjects following a 7-day diet journaling period. The purpose of the experiment is to evaluate potential differences in lipid concentrations/metabolism between bipolar and control subjects with the ability to correct for dietary intake, age, gender and medication use.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Subjects were subjected to different dietary interventions. Indivduals (A1 to A19) were either randomized to a isocaloric diet with either 40-45% saturated fat diet or 40-45% monounsaturated fat diet for 4 weeks. Plasma was sampled at baseline and after 4 weeks on the diet in the fasting state. Multiple clinical values (Weight, blood pressure, pulse,total cholesterol, HDL, LDL and triglycerides) and hyperinsulinemic euglycemic clamps were assessed. Alternatively (XS-3 to XS 43) were provided a diet that was 2000 calories above the estimated isocaloric state for 2 weeks. Multiple clinical values (Weight, blood pressure, pulse,total cholesterol, HDL, LDL and triglycerides) were determined along with body composition, insulin and glucose values.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Effect of high fat diet and streptozotocin treatment on neuropathy
STUDY_TYPE
MS analysis
STUDY_SUMMARY
C57BL6 male mice were fed either a control 10% fat (RD D12540-B) or a high fat 60% fat (RD 12492) diet from 5 wk age. STZ was given to some groups at 12 wk age. Chow was reversed in some groups (DR) from 60% HF to 10 % HF at 16 wk age. Mice were euthanized at either 16 wk or 24 wk age. Neuropathy phenotyping occured prior to all harvests.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Stable clones of Control lentiviral (CLV) or lentiviral Noxa knockdown cells (NshLV7) (as described in Lowman et al, 2010) were counted at T-18hr and 60E6 cells were resuspended in 100ml of fresh complete medium. At T0 cells were counted again and 20E6 were collected into triplicate tubes. Cells were washed 1X with ice cold PBS and resuspended in 300ul ice cold methanol. Cells were then snap frozen in liquid nitrogen and stored at -80C. An additional 10E6 cells were collected for protein concentration and Western blot analysis.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Human oral keratinocytes growth and proliferation based on culture medium volume
STUDY_TYPE
MS analysis
STUDY_SUMMARY
We seeded cells at density of 500k/T75 and cultured them at two different medium volume, one at 30ml, the other at 15ml. Culture medium is composed of 1x EDGS and 0.06mM calcium. We changed medium every day for 30ml culture, and every two days for 15ml culture. We collected spent medium when we changed medium. The collected spent medium was filtered through low protein binding 0.22um pore size filter and then stored at -80 degree C. For OA and SMT, spent medium was collected on the same day of D5 and D9 after cell seeding as marked on the tubes. For GK samples, 15ml and 30ml cultures were collected when cells reached at around 90% confluence, that is D5 for 15ml and D6 for 30 ml culture. The numbers 151, 152 were duplicated cell cultures in two T75s, same for 301 and 302. One major differences among GK, OA, and SMT is GK was from frozen cells; OA and SMT were fresh cells that were never frozen. Blank15 and Blank30 were complete medium without cells incubating in incubator for two days for Blank15 and one day for Blank30. Medium was collected in the same manner as others.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Metabolites produced by strains associated with inflammation
STUDY_TYPE
MS analysis
STUDY_SUMMARY
EXPERIMENT 1: identify commonalities and differences between species at late log phase. EXPERIMENT 2: identify commonalities and differences within a species in function of the media used for the subset of bacteria cultured in more than one media. EXPERIMENT 3: identify commonalities and differences within a species in function of the growth phase for the subset of strains for which more than one time point was taken during the growth phase. Factor 1: growth phase for this slow growers as defined by early, mid and late log phase. Factor 2:rich media used for growth which are either NOS or OMIZ supplemented or not of TPP (thiamine pyrophosphate) a required supplement for some strains. Factor 3: cell pellet and supernatant of culture in which bacetria excrete small molecules. Factor 4. the bacterial species. All those bacteria come from the same genus and have been isolated in function of inflmmatory conditions in human.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Lanthanide-mineral induced alteration of bile acid metabolism in a murine model of steatohepatitis
STUDY_TYPE
MS analysis
STUDY_SUMMARY
120 mice (equal number of males and females) were randomized into 3 equal groups. One group is on a high-fat "Western-style" diet (HFWD) alone, a second group is on HFWD supplemented with lanthanides and calcium, and a third control group is supplemented with calcium alone. At study termination (18 months) we will harvest hepatocytes and colonic enterocytes for evaluation of epithelial gene expression patterns. We will also harvest cecal contents and feces for microbial profiling by 16S rRNA pyrosequencing. For this small pilot proposal, we wish to add an untargeted metabolomic analysis component. We will harvest liver (right medial lobe with gall bladder), serum, and feces. We will assay representative liver/gall bladder samples (8 from the HFWD group and 8 from the lanthanide/calcium supplemented group). Remaining liver samples and the serum and feces will be archived for future investigation. Liver is being targeted first since both steatohepatitis and hepatocellular carcinoma were seen in our previous study in mice on HFWD. Additionally, alterations of bile acid profiles and bile acid metabolism have been associated with both steatohepatitis and hepatic cancers.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Differences in bile acids composition between ASCL5 knockout and floxed mice.
STUDY_TYPE
MS analysis
STUDY_SUMMARY
Understand the differences in Bile Acid composition between knockout and floxed mice at each intestinal segment. Also difference in metabolites between these two groups at each level of the intestine.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Pilot metabolomics study of aromatase inhibitor associated arthralgias
STUDY_TYPE
MS analysis
STUDY_SUMMARY
The goal of the experiment is untargeted metabolomic and shotgun lipidomic profiling of serum samples collected from 50 patients before patients initiated therapy with an aromatase inhibitor and again after 3 months of aromatase inhibitor therapy. Half of the patients discontinued treatment within 6 months because of development of arthralgias during therapy and half remained on therapy for at least 24 months without development of significant arthralgias. We plan to analyse effects of AI therapy on metabolomic and lipidomic profiles, and to investigate associations between changes in profiles and development of symptoms.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Brain-Immune system-Gut Interaction in Chronic Mild Stress (CMS +/- Lacto)
STUDY_TYPE
MS analysis
STUDY_SUMMARY
Mice were devided into three groups (Naive untreated, Stressed untreated, Stressed + Lacto). The stressed groups were subjected to unpredictable chronic mild stress for seven weeks. Three weeks into the protocol, the +Lacto groups were administered probiotic Lactobacillus daily.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Cytokines correlation with metabolomic profiling of psoriatic and normal skin
STUDY_TYPE
MS analysis
STUDY_SUMMARY
These experiments are cytokine stimulations (TNF, IL-17, IFNg) of three keratinocyte lines (HAHA, PAK and BS4). Aim is to determine the metabolic changes induced by these cytokines and correlate with metabolomic profiling of psoriatic, uninvolved and normal skin.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Differences in metabolism in mouse embryonic fibroblasts (control vs SCF-beta-TrCP knockout)
STUDY_TYPE
MS analysis
STUDY_SUMMARY
Mouse embryonic fibroblasts were grown in DMED supplemented with 10%FBS. The same number of cells were plated in eight 6cm dishes. When the cells were ~70% confluent, four dishes received ethanol (carrier) and the other four received tamoxifen (1uM final) to induce knockout. The cells and media were harvested 4 days later. The media harvested from control and knockout dishes will be compared with the starting medium. The cells were washed with cold PBS twice while they are attached to the dishes. The whole dish with cells attached were immediately frozen in dry ice and wrapped with aluminum foil and stored at -80C.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
NIH 3T3 fibroblast cells with Ceftriaxone Treatment
STUDY_TYPE
MS analysis
STUDY_SUMMARY
NIH 3T3 cells were plated at 1.5million cells per 10cM dish into 12 10cm dishes. 24hrs post plating media was changed on all plates. At the time of media change, 4 dishes were treated with a final concentration of 50uM ceftriaxone (24hrs ceftriaxone n=4). 23 hrs post media change, 4 separate dishes were treated with 50uM ceftriaxone for 1hr (1hr ceftriaxone n=4). 4 dishes were untreated (0hr, basal, n=4). 24 hrs post media change, media was quickly removed from all 12 plates, each plate was rapidly washed with MilliQ H2O and rapidly frozen with liquid nitrogen poured directly into the dishes. All plates were transferred to dry ice and stored at -80 until shipped.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Short chain Fatty Acid (SCFA) analysis in HIV patients
STUDY_TYPE
MS analysis
STUDY_SUMMARY
We hypothesize that a microbiome enriched with anaerobes in HIV leads to SCFA production and immunomodulatory effects. The goal of the experiment is evaluating bacterial metabolic pathways leading to production of SCFA. DLCO stands for Diffusing capacity of the lungs for carbon monoxide.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Plasma from young adult mice, fasted 4 hr prior to bleeding. Key comparisons: Snell dwarf vs Snell normal. GHRKO KO vs WT. PAPPA KO vs Het. And two factor ANOVA: LivGHR KO, LivGHR WT vs GHRKO and GHRWT. Consistency between Snell, GHRKO, and PAPPA will be a major theme in the analysis.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Effect of DASH Diet on Gut Microbiome (SCFA from stool)
STUDY_TYPE
MS analysis
STUDY_SUMMARY
This research will examine the effect of the currently recommended DASH diet versus a Vegetarian DASH diet on the gut microbiome and risk for cardiovascular disease in pre-hypertensive obese African American women. We will define the gut microbiota profile, short chain fatty acid production, breath hydrogen/methane response, plasma lipopolysaccharide production and other biomarkers of inflammation in response to diet type in obese African American pre-hypertensive females at baseline and following placement on the traditional DASH plan or DASH Vegetarian diet. We will also define these parameters in African American women adhering to a Vegetarian or Vegan Diet. Our goal is to determine how the gut microbiome modulates host physiology and immune function in response to diet type. By evaluating the effect of a recommended DASH dietary pattern versus a Vegetarian DASH plan on the gut microbiome and its fermentation products, we aim to identify novel information about how these diet types strategically reduce cardiovascular disease risk through gut:microbiota:host interaction.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
EMAIL
mkachman@med.umich.edu
PHONE
(734) 232-8175
NUM_GROUPS
5
TOTAL_SUBJECTS
13
STUDY_COMMENTS
We will define the gut microbiota profile, short chain fatty acid production, breath hydrogen/methane response, plasma lipopolysaccharide production and other biomarkers of inflammation in response to diet type in obese African American pre-hypertensive females at baseline and following placement on the traditional DASH plan or DASH Vegetarian diet. We will also define these parameters in African American women adhering to a Vegetarian or Vegan Diet. Our goal is to determine how the gut microbiome modulates host physiology and immune function in response to diet type. By evaluating the effect of a recommended DASH dietary pattern versus a Vegetarian DASH plan on the gut microbiome and its fermentation products, we aim to identify novel information about how these diet types strategically reduce cardiovascular disease risk through gut:microbiota:host interaction.
Metabolic effects of weight reduction of very low energy diet vs dietary counseling
STUDY_TYPE
MS analysis
STUDY_SUMMARY
The goal of the study is to assess the relative efficacy of a very low energy diet (VLED) using liquid meal replacement vs. standard of care dietary counseling and education (DCE) on the metabolic effects of weight reduction in the obese, subfertile population and assess ovulation and time to conception in these women. Subfertile women were recruited for this study. They completed an OGTT at baseline and again after completing a very low energy diet intervention.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Metabolomic Profiles of Recovery from Traumatic Brain Injury
STUDY_TYPE
MS analysis
STUDY_SUMMARY
We hypothesize that differences between the metabolome of TBI patients achieving full recovery at 3 months post-injury and those with protracted recovery will provide insights into the biology of recovery and yield novel biomarkers for predicting protracted recovery. To test our hypothesis, we will perform a case-control study examining the metabolomic profile of 128 TBI patients, 18 years and older, who either have complete functional recovery at 3 months post-injury or have functional decline at 3 months post-injury. Subjects were selected from an ongoing prospective cohort of traumatic brain injury (Head Injury Serum Markers for Assessing Response to Trauma, HeadSMART. Funding for HeadSMART was provided by ImmunArray.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Replicate populations of Aedes albopictus were reared under diapause-inducing short day photoperiod (8h light: 16h dark) and diapause-averting long day photoperiod (16h light:8h dark). Eggs were collected from each replicate and snap-frozen 11d post-oviposition. We hope to characterize the metabolomic and lipidomic profiles of diapausing eggs relative to non-diapause eggs.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Metabolite-phenotype link in X-linked Adrenoleukodystrophy (fibroblast cell culture)
STUDY_TYPE
MS analysis
STUDY_SUMMARY
Untargeted metabolomics of control, AMN and ALD patient-derived fibroblasts. Fibroblasts cultured in DMEM with 15%FBS and antibiotic (pen/strep) in 100mm petridishes (1million/dish). After 24h cultures supplemented with fresh media (DMEM+15%FBS+antibiotic) for 3hr
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Metabolite-phenotype link in X-linked Adrenoleukodystrophy (part II)
STUDY_TYPE
MS analysis
STUDY_SUMMARY
Untargeted metabolomics of control, AMN and ALD patient-derived fibroblasts. Human Postmortem brain tissue were obtained from NICHD Brain Bank. Brain regions were directed by the neuropathologist at Henry Ford Health System and sample tissue were immediately frozen at -80C until shipping to the UMICH Core.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Metabolomics of mice inoculated with human microbiota
STUDY_TYPE
MS analysis
STUDY_SUMMARY
Mice were inoculated with human microbiota. Peripheral blood was collected using superficial temporal phlebotomy into a tube containing EDTA-K2. Tubes were then inverted 5 times and placed on ice for no longer than one hour. Samples were centrifuged at 1500rcf for 15 minutes. Supernatant was transferred and quantified with a pipette. Tubes were placed on dry ice for between 10 minutes to an hour andl stored at -80C until shipped on dry ice. All steps during processing were performed in batches containing mulitple treatment groups.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Blood was collected from the facial vein of humanized mice immediately prior to euthansia via CO2 inhalation. Blood sat at room temperature for 20 minutes, and then was centrifuged at 12000g for 10 minutes at 4 C. Serum was removed to a new eppendorf tube and immediately placed on ice, and then samples were subsequently stored at - 20 C until the present.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Metabolomics of mice inoculated with human stool (part III).
STUDY_TYPE
MS analysis
STUDY_SUMMARY
Mice were inoculated with human stool samples from donors in a high gene copy number group or low gene copy number group. After several weeks, cecal contents were collected and frozen at -80. Aliquots were made on dry ice and then stored at -80 until shipment on dry ice. Analysis of short chain fatty acids (SCFA) of cecal content was performed.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Metabolomics of cilia and modulation of renal microcirculation
STUDY_TYPE
MS analysis
STUDY_SUMMARY
Explore and explain the mechanism of regulation of metabolism biomarkers to modulate renal microcirculation. 1 - let rats rest for 5 days. 2 - test basal glucose and plasma. Store plasma in -20C for one day then transfer to -80. 3 - inject STZ 50mg/kg ip. 4 - after 3 days, check for increased glucose and extract plasma for early stage diabetic sample >300 mg/dl. Store in -20C and then -80C. 5 - one month after initial injection, extract plasma and store in -20C and then -80C.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Tubuloglomerular feedback and salt-sensitive hypertension
STUDY_TYPE
MS analysis
STUDY_SUMMARY
Collect whole blood in tubes containing EDTA, gently invert tubes 10 times and cool as soon as practical on ice. Centrifuge to separate plasma as soon as practical, transfer to appropriately labeled tubes, and freeze immediately. I test basal glucose and plasma store plasma in -20C for one day then transfer to -80C. The next day, inject STZ 60 mg/kg ip. After 3 days, check for increased glucose and extract plasma for early stage diabetic sample >300 mg/dl. Store in -20C and then -80C. 30 days after initial injection, extract plasma and store in -20C and then -80C.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
One year caloric restriction (CR) compared to ad lib (AL) feeding on metabolic and clinical parameters to assess association with intrinsic oxidative capacity. High and low capacity running rats (HCR and LCR) were randomized to ad lib feeding vs. 40% caloric restriction starting at 8 weeks of age. Experiment was continued for 52 weeks when blood and tissue were collected. Exercise capacity, CLAMS assessment of fuel utilization and clinical parameters were determined at 8 weeks, 8 months and 12 months of age. Tissue was collected in the fed (2 hours after re-feeding) or fasted stated all groups.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Metabolic effects of novel aldehyde dehydrogenase inhibitors (ALDH) inhibitors
STUDY_TYPE
MS analysis
STUDY_SUMMARY
Effect of novel aldehyde dehydrogenase inhibitors. Before an experiment medium was replaced to medium without glucose with addition of labeled glucose on C13. Next, cells were treated with ALDH inhibitors 673 or 773 for 1, 4, or 8 hr (673&773-Jan26)
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Michigan Biomarkers for Refractory Depression (Bluebird) metabolomics pilot study
STUDY_TYPE
MS analysis
STUDY_SUMMARY
The goal of the project is discovery of clinical useful biomarkers for treatment-resistant depression. All participants were undergoing electroconvulsive therapy (ECT) for treatment-resistant depression (major depressive disorder or bipolar disorder) in 2012-2014. All subjects were Caucasian except BB060, who was Asian. Samples were collected from each subject at baseline just before the first ECT treatment (Time Point T0) and approximately 3 weeks later just before the tenth ECT treatment (Time Point T2). Whole blood was drawn in the morning in a fasted state (at least 7 hours) through an intravenous catheter or butterfly needle into 6-mL EDTA tubes (Lavender Top, Becton Dickinson Vacutainer K2EDTA additive blood collection tube, part #367863) and transported to the processing lab at the Michigan Clinical Research Unit within 30 minutes. Plasma was isolated by centrifugation for 10 minutes at 2000G at 4C. Plasma from multiple tubes was pooled and aliquotted in 200 uL volumes into 2-mL screw-cap cryovials and frozen at -80C.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Nuclear magnetic resonance-based metabolomics approach to evaluate the prevention effect of Camellia nitidissima Chi on colitis-associated carcinogenesis
STUDY_TYPE
Original Research
STUDY_SUMMARY
Colorectal cancer (CRC) is one of the most common malignant tumors worldwide, occurring in the colon or rectum portion of large intestine. With marked antioxidant, anti-inflammation and anti- tumor activities, Camellia nitidissima Chi has been used as an effective treatment of cancer. The azoxymethane/dextran sodium sulfate (AOM/DSS) induced CRC mice model was established and the prevention effect of Camellia nitidissima Chi extracts on the evolving of CRC was evaluated by gross examination, histopathological inspection, serum biochemistry analysis, combined with nuclear magnetic resonance (NMR)-based metabolomics and correlation network analysis. The results showed that Camellia nitidissima Chi extracts could significantly inhibit AOM/DSS induced CRC, relieve the colonic pathology and ameliorate the serum biochemistry, and could significantly reverse the disturbed metabolism towards the normal state. Moreover, the butanol fraction showed a better efficiency than the water-soluble fraction of Camellia nitidissima Chi. The study pave the way for further development of Camellia nitidissima Chi extracts as a potent CRC inhibitor.
Identifying metabolic adaptations characteristic of multiple myeloma cells via targeted sphingolipids concentrations from bone marrow and peripheral plasma
STUDY_SUMMARY
Will be assessing the targeted sphingolipids concentrations of high risk versus low risk smoldering myeloma patients based on peripheral blood plasma and bone marrow plasma.
INSTITUTE
Mayo Clinic
LAST_NAME
Gonsalves
FIRST_NAME
Wilson
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Identifying metabolic adaptations characteristic of multiple myeloma cells via amino acids concentrations from bone marrow plasma
STUDY_SUMMARY
Will be assessing the targeted amino acids concentrations of high risk versus low risk smoldering myeloma patients based on peripheral blood plasma and bone marrow plasma.
INSTITUTE
Mayo Clinic
LAST_NAME
Gonsalves
FIRST_NAME
Wilson
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Large Untargeted Profiling of Myelin to Enhance Recovery of Function after SCI
STUDY_SUMMARY
Tissue is from adult mouse spinal cord (SC). We are submitting these samples for Untargeted Profiling (unbiased metabolomics assay) and for lipid analysis. The lipid assays we request are 1) free fatty acid composition of lipids; 2) free fatty acid panel; 3) cholesterol concentration (free and bound); 4) Ceramides, including galactosyl and glucosyl; 5) sphingomyelin. The Untargeted profiling is our top priority, followed by the lipid assays as listed. All samples were snap frozen at the point of harvest and approximate weights are provided. The samples are submitted as intact pieces of tissue. There are 20 samples total, n=5 for each group that includes LF (low fat diet); HF (high fat diet); HFHS (high fat high sucrose diet); and Keto (ketogenic diet).
INSTITUTE
Mayo Clinic
LAST_NAME
Scarisbrick
FIRST_NAME
Isobel
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Targeted FFA Composition of Myelin to Enhance Recovery of Function after SCI
STUDY_SUMMARY
Tissue is from adult mouse spinal cord (SC). We are submitting these samples for Untargeted Profiling (unbiased metabolomics assay) and for lipid analysis. The lipid assays we request are 1) free fatty acid composition of lipids; 2) free fatty acid panel; 3) cholesterol concentration (free and bound); 4) Ceramides, including galactosyl and glucosyl; 5) sphingomyelin. The Untargeted profiling is our top priority, followed by the lipid assays as listed. All samples were snap frozen at the point of harvest and approximate weights are provided. The samples are submitted as intact pieces of tissue. There are 20 samples total, n=5 for each group that includes LF (low fat diet); HF (high fat diet); HFHS (high fat high sucrose diet); and Keto (ketogenic diet).
INSTITUTE
Mayo Clinic
LAST_NAME
Scarisbrick
FIRST_NAME
Isobel
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Targeted NEFA Panel of Myelin to Enhance Recovery of Function after SCI
STUDY_SUMMARY
Tissue is from adult mouse spinal cord (SC). We are submitting these samples for Untargeted Profiling (unbiased metabolomics assay) and for lipid analysis. The lipid assays we request are 1) free fatty acid composition of lipids; 2) free fatty acid panel; 3) cholesterol concentration (free and bound); 4) Ceramides, including galactosyl and glucosyl; 5) sphingomyelin. The Untargeted profiling is our top priority, followed by the lipid assays as listed. All samples were snap frozen at the point of harvest and approximate weights are provided. The samples are submitted as intact pieces of tissue. There are 20 samples total, n=5 for each group that includes LF (low fat diet); HF (high fat diet); HFHS (high fat high sucrose diet); and Keto (ketogenic diet).
INSTITUTE
Mayo Clinic
LAST_NAME
Scarisbrick
FIRST_NAME
Isobel
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Targeted Cholesterol Profiling of Myelin to Enhance Recovery of Function after SCI
STUDY_SUMMARY
Tissue is from adult mouse spinal cord (SC). We are submitting these samples for Untargeted Profiling (unbiased metabolomics assay) and for lipid analysis. The lipid assays we request are 1) free fatty acid composition of lipids; 2) free fatty acid panel; 3) cholesterol concentration (free and bound); 4) Ceramides, including galactosyl and glucosyl; 5) sphingomyelin. The Untargeted profiling is our top priority, followed by the lipid assays as listed. All samples were snap frozen at the point of harvest and approximate weights are provided. The samples are submitted as intact pieces of tissue. There are 20 samples total, n=5 for each group that includes LF (low fat diet); HF (high fat diet); HFHS (high fat high sucrose diet); and Keto (ketogenic diet).
INSTITUTE
Mayo Clinic
LAST_NAME
Scarisbrick
FIRST_NAME
Isobel
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Targeted Sphingolipids Panel of Myelin to Enhance Recovery of Function after SCI
STUDY_SUMMARY
Tissue is from adult mouse spinal cord (SC). We are submitting these samples for Untargeted Profiling (unbiased metabolomics assay) and for lipid analysis. The lipid assays we request are 1) free fatty acid composition of lipids; 2) free fatty acid panel; 3) cholesterol concentration (free and bound); 4) Ceramides, including galactosyl and glucosyl; 5) sphingomyelin. The Untargeted profiling is our top priority, followed by the lipid assays as listed. All samples were snap frozen at the point of harvest and approximate weights are provided. The samples are submitted as intact pieces of tissue. There are 20 samples total, n=5 for each group that includes LF (low fat diet); HF (high fat diet); HFHS (high fat high sucrose diet); and Keto (ketogenic diet).
INSTITUTE
Mayo Clinic
LAST_NAME
Scarisbrick
FIRST_NAME
Isobel
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Targeted Galactosyl Sphingolipids Concentrations of Myelin to Enhance Recovery of Function after SCI
STUDY_SUMMARY
Tissue is from adult mouse spinal cord (SC). We are submitting these samples for Untargeted Profiling (unbiased metabolomics assay) and for lipid analysis. The lipid assays we request are 1) free fatty acid composition of lipids; 2) free fatty acid panel; 3) cholesterol concentration (free and bound); 4) Ceramides, including galactosyl and glucosyl; 5) sphingomyelin. The Untargeted profiling is our top priority, followed by the lipid assays as listed. All samples were snap frozen at the point of harvest and approximate weights are provided. The samples are submitted as intact pieces of tissue. There are 20 samples total, n=5 for each group that includes LF (low fat diet); HF (high fat diet); HFHS (high fat high sucrose diet); and Keto (ketogenic diet).
INSTITUTE
Mayo Clinic
LAST_NAME
Scarisbrick
FIRST_NAME
Isobel
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Targeted Sphinomyelin Panel of Myelin to Enhance Recovery of Function after SCI
STUDY_SUMMARY
Tissue is from adult mouse spinal cord (SC). We are submitting these samples for Untargeted Profiling (unbiased metabolomics assay) and for lipid analysis. The lipid assays we request are 1) free fatty acid composition of lipids; 2) free fatty acid panel; 3) cholesterol concentration (free and bound); 4) Ceramides, including galactosyl and glucosyl; 5) sphingomyelin. The Untargeted profiling is our top priority, followed by the lipid assays as listed. All samples were snap frozen at the point of harvest and approximate weights are provided. The samples are submitted as intact pieces of tissue. There are 20 samples total, n=5 for each group that includes LF (low fat diet); HF (high fat diet); HFHS (high fat high sucrose diet); and Keto (ketogenic diet).
INSTITUTE
Mayo Clinic
LAST_NAME
Scarisbrick
FIRST_NAME
Isobel
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Targeted TCA Panel of Myelin to Enhance Recovery of Function after SCI
STUDY_SUMMARY
Tissue is from adult mouse spinal cord (SC). We are submitting these samples for Untargeted Profiling (unbiased metabolomics assay) and for lipid analysis. The lipid assays we request are 1) free fatty acid composition of lipids; 2) free fatty acid panel; 3) cholesterol concentration (free and bound); 4) Ceramides, including galactosyl and glucosyl; 5) sphingomyelin. The Untargeted profiling is our top priority, followed by the lipid assays as listed. All samples were snap frozen at the point of harvest and approximate weights are provided. The samples are submitted as intact pieces of tissue. There are 20 samples total, n=5 for each group that includes LF (low fat diet); HF (high fat diet); HFHS (high fat high sucrose diet); and Keto (ketogenic diet).
INSTITUTE
Mayo Clinic
LAST_NAME
Scarisbrick
FIRST_NAME
Isobel
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
The goal is to look at measures of overall metabolic state in relationship to hormonal environment and measures of mood/depression or cognitive function (behavioral and functional MRI images). There are some relationships in this data set between glucose/insulin levels and cognitive function, and we would like to use the untargeted assays to further investigate this relationship. Factors related to visual/spatial memory are included in the design. Factors 1 and 2 (Left Hippocampus, Right Hippocampus) are levels of activation in the hippocampus during a visual memory task, (data missing for some of the samples). Factors 3-5 (BVMT % Retained, BVMT Learning T, BVMT Delay T) are results from a cognitive test of spatial memory function.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Integrated nutrigenomic and metabolomic analysis of Africans with variable diet
STUDY_TYPE
MS analysis
STUDY_SUMMARY
Untargeted metabolic profiling and lipidomics profiling will be used to characterize a broad array of metabolites from plasma in 450 ethnically diverse individuals from Ethiopia, Tanzania, and Botswana with diverse diets. Mass spectrometry will be used to quantify metabolites previously found to be associated with cardiometabolic risk as well as the most informative metabolites from the untargeted screen. We will test for association of selected biomarkers with diet, geography, ancestry, and phenotypic variation. Metabolites obtained will be correlated with diet as well as clinical and anthropometric phenotypes. Using existing tools, we will assemble metabolites that associate with the various phenotypes into pathways and larger networks to provide insights into factors that relate to cardiometabolic health and disease. Finally, we will integrate metabolic and phenotypic data with genetic data from the SNP array and with high coverage whole genome sequence data. We will identify loci that play a role in local adaptation to diverse diets and will identify genetic variants associated with metabolite levels (mQTLs) and with the phenotypic traits listed above.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
EMAIL
mkachman@med.umich.edu
PHONE
(734) 232-8175
NUM_GROUPS
43
TOTAL_SUBJECTS
450
STUDY_COMMENTS
Targeted mass spectrometry will be used to quantify metabolites previously found to be associated with cardiometabolic risk as well as the most informative metabolites from the untargeted screen. We will test for association of selected biomarkers with diet, geography, ancestry, and phenotypic variation. Metabolites obtained will be correlated with diet as well as clinical and anthropometric phenotypes. Using existing tools, we will assemble metabolites that associate with the various phenotypes into pathways and larger networks to provide insights into factors that relate to cardiometabolic health and disease. Finally, we will integrate metabolic and phenotypic data with genetic data from the SNP array and with high coverage whole genome sequence data. We will identify loci that play a role in local adaptation to diverse diets and will identify genetic variants associated with metabolite levels (mQTLs) and with the phenotypic traits listed above.
SJGBM2 and MGG8 glioma cells were stable transfected with IDH1-R132H mutated. The expression of IDH1-R132H was confirmed by Western Blot assay. The aim of this project is analyze the production of 2HG in the stable transfected cells (SJGBM-IDH1m and MGG8-IDH1m) compared with the control group WT.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Human cord blood serum samples (200) were provided by David Christiani. The 200 study samples, total pool samples, and external CHEAR Plasma Reference Material samples were prepared and analyzed using the Biocrates AbsoluteIDQ p180 Kit.
Human cord blood serum samples (200) were provided by David Christiani. The 200 study samples, total pool samples, and external CHEAR Plasma Reference Material samples were prepared for NMR data collection and signals were library matched to metabolites to determine semi-quantitative concentration data using Chenomx NMR Suite 8.1.
INSTITUTE
RTI International
LAST_NAME
Fennell
FIRST_NAME
Timothy
ADDRESS
3040 E Cornwallis Rd, Durham, NC 27709
EMAIL
fennell@rti.org
PHONE
9194852781
TOTAL_SUBJECTS
200
STUDY_COMMENTS
Due to sample volume limitations: study samples, study pools, and CHEAR reference samples were prepared using 150 uL of sample and diluted with 100 ul of 0.9% Saline buffer. This is a deviation from the CHEAR Proficiency testing in which 400 ul of CHEAR reference sample was used and diluted with 300 uL of 0.9% Saline buffer. Samples were then transfered into a 3 mm NMR tube, in this study, as opposed to a 5 mm NMR tube for the Proficiency testing. Data for this study were acquired on a 600 MHz Bruker NMR spectrometer. Data for the procficiency testing were acquired on a 700 MHz Bruker NMR spectrometer.
Obesity and marrow and marrow adipose tissue (MAT) metabolomics
STUDY_TYPE
MS analysis
STUDY_SUMMARY
Male C57Bl6j mice were fed HFD for 16-20 weeks and marrow adipose tissue (MAT) and bone marrow collected to evaluate lipid content/lipid type. In addition, marrow evaluations for glycolysis/TCA cycle and acylcarnitines will be performed.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
"PA" samples: matched plasma and muscle samples from an obese subject mild-intensity exercise training study, V1 is the first visit (untrained), V4 is post 3 months training, 1 day after exercise and V5 is post 3 months training, 3 days after last exercise.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Innovative and novel therapies are urgently needed for the treatment of patients with severe asthma, especially those who are refractory to standard-of-care bronchodilators and inhaled corticosteroids. The Zeki lab is investigating the role of the mevalonate (MA) pathway, in the pathogenesis of airway inflammation and remodeling. Although statins all inhibit HMGCR in the same manner in terms of enzyme binding site, the statins’ varied physiochemical properties with respect to their polarity (i.e. lipophilicity) result in very different immune and lipid effects. The major significance of this work is to advance a new class of inhaler therapies for asthma; the statins which work by an entirely different mechanism than current ICS/LABA mainstays. Evidence suggests that statins may have an additive benefit to corticosteroids in asthma, thereby confirming a unique mechanism, namely via MVA pathway inhibition. This becomes particularly important in the severe asthma population which is highly corticosteroid-resistant, is poorly controlled with high exacerbation rates and hospitalizations, and has the highest healthcare costs of all asthma phenotypes. In essence, the potential public health impact of even an incremental improvement in asthma symptom control cannot be underestimated. Even the prevention of 1 asthma attack preserves lung function and reduces the adverse personal and financial impact. This study aimed to determine if statin polarity affects airway drug concentration and systemic drug absorption and to determine the effect of inhaled statins on naïve airway immune cell populations and alveolar-capillary membrane and epithelial barrier integrity in healthy rhesus monkeys. In this particular component of the study, we investigated the metabolic effects resulting from the use of statins in these healthy rhesus monkeys. Specifically, the Newman lab analyzed for lipid mediator (oxylipin, endocannabinoid, fatty acid, and nitro lipid) in lung and trachea tissue, plasma, and BAL and bile acid changes in the lung and trachea tissue and plasma.
Innovative and novel therapies are urgently needed for the treatment of patients with severe asthma, especially those who are refractory to standard-of-care bronchodilators and inhaled corticosteroids. The Zeki lab is investigating the role of the mevalonate (MA) pathway, in the pathogenesis of airway inflammation and remodeling. Although statins all inhibit HMGCR in the same manner in terms of enzyme binding site, the statins’ varied physiochemical properties with respect to their polarity (i.e. lipophilicity) result in very different immune and lipid effects. The major significance of this work is to advance a new class of inhaler therapies for asthma; the statins which work by an entirely different mechanism than current ICS/LABA mainstays. Evidence suggests that statins may have an additive benefit to corticosteroids in asthma, thereby confirming a unique mechanism, namely via MVA pathway inhibition. This becomes particularly important in the severe asthma population which is highly corticosteroid-resistant, is poorly controlled with high exacerbation rates and hospitalizations, and has the highest healthcare costs of all asthma phenotypes. In essence, the potential public health impact of even an incremental improvement in asthma symptom control cannot be underestimated. Even the prevention of 1 asthma attack preserves lung function and reduces the adverse personal and financial impact. This study aimed to determine if statin polarity affects airway drug concentration and systemic drug absorption and to determine the effect of inhaled statins on naïve airway immune cell populations and alveolar-capillary membrane and epithelial barrier integrity in healthy rhesus monkeys. In this particular component of the study, we investigated the metabolic effects resulting from the use of statins in these healthy rhesus monkeys. Specifically, the Newman lab analyzed for lipid mediator (oxylipin, endocannabinoid, fatty acid, and nitro lipid) in lung and trachea tissue, plasma, and BAL and bile acid changes in the lung and trachea tissue and plasma.
Innovative and novel therapies are urgently needed for the treatment of patients with severe asthma, especially those who are refractory to standard-of-care bronchodilators and inhaled corticosteroids. The Zeki lab is investigating the role of the mevalonate (MA) pathway, in the pathogenesis of airway inflammation and remodeling. Although statins all inhibit HMGCR in the same manner in terms of enzyme binding site, the statins’ varied physiochemical properties with respect to their polarity (i.e. lipophilicity) result in very different immune and lipid effects. The major significance of this work is to advance a new class of inhaler therapies for asthma; the statins which work by an entirely different mechanism than current ICS/LABA mainstays. Evidence suggests that statins may have an additive benefit to corticosteroids in asthma, thereby confirming a unique mechanism, namely via MVA pathway inhibition. This becomes particularly important in the severe asthma population which is highly corticosteroid-resistant, is poorly controlled with high exacerbation rates and hospitalizations, and has the highest healthcare costs of all asthma phenotypes. In essence, the potential public health impact of even an incremental improvement in asthma symptom control cannot be underestimated. Even the prevention of 1 asthma attack preserves lung function and reduces the adverse personal and financial impact. This study aimed to determine if statin polarity affects airway drug concentration and systemic drug absorption and to determine the effect of inhaled statins on naïve airway immune cell populations and alveolar-capillary membrane and epithelial barrier integrity in healthy rhesus monkeys. In this particular component of the study, we investigated the metabolic effects resulting from the use of statins in these healthy rhesus monkeys. Specifically, the Newman lab analyzed for lipid mediator (oxylipin, endocannabinoid, fatty acid, and nitro lipid) in lung and trachea tissue, plasma, and BAL and bile acid changes in the lung and trachea tissue and plasma.
Innovative and novel therapies are urgently needed for the treatment of patients with severe asthma, especially those who are refractory to standard-of-care bronchodilators and inhaled corticosteroids. The Zeki lab is investigating the role of the mevalonate (MA) pathway, in the pathogenesis of airway inflammation and remodeling. Although statins all inhibit HMGCR in the same manner in terms of enzyme binding site, the statins’ varied physiochemical properties with respect to their polarity (i.e. lipophilicity) result in very different immune and lipid effects. The major significance of this work is to advance a new class of inhaler therapies for asthma; the statins which work by an entirely different mechanism than current ICS/LABA mainstays. Evidence suggests that statins may have an additive benefit to corticosteroids in asthma, thereby confirming a unique mechanism, namely via MVA pathway inhibition. This becomes particularly important in the severe asthma population which is highly corticosteroid-resistant, is poorly controlled with high exacerbation rates and hospitalizations, and has the highest healthcare costs of all asthma phenotypes. In essence, the potential public health impact of even an incremental improvement in asthma symptom control cannot be underestimated. Even the prevention of 1 asthma attack preserves lung function and reduces the adverse personal and financial impact. This study aimed to determine if statin polarity affects airway drug concentration and systemic drug absorption and to determine the effect of inhaled statins on naïve airway immune cell populations and alveolar-capillary membrane and epithelial barrier integrity in healthy rhesus monkeys. In this particular component of the study, we investigated the metabolic effects resulting from the use of statins in these healthy rhesus monkeys. Specifically, the Newman lab analyzed for lipid mediator (oxylipin, endocannabinoid, fatty acid, and nitro lipid) in lung and trachea tissue, plasma, and BAL and bile acid changes in the lung and trachea tissue and plasma.
Innovative and novel therapies are urgently needed for the treatment of patients with severe asthma, especially those who are refractory to standard-of-care bronchodilators and inhaled corticosteroids. The Zeki lab is investigating the role of the mevalonate (MA) pathway, in the pathogenesis of airway inflammation and remodeling. Although statins all inhibit HMGCR in the same manner in terms of enzyme binding site, the statins’ varied physiochemical properties with respect to their polarity (i.e. lipophilicity) result in very different immune and lipid effects. The major significance of this work is to advance a new class of inhaler therapies for asthma; the statins which work by an entirely different mechanism than current ICS/LABA mainstays. Evidence suggests that statins may have an additive benefit to corticosteroids in asthma, thereby confirming a unique mechanism, namely via MVA pathway inhibition. This becomes particularly important in the severe asthma population which is highly corticosteroid-resistant, is poorly controlled with high exacerbation rates and hospitalizations, and has the highest healthcare costs of all asthma phenotypes. In essence, the potential public health impact of even an incremental improvement in asthma symptom control cannot be underestimated. Even the prevention of 1 asthma attack preserves lung function and reduces the adverse personal and financial impact. This study aimed to determine if statin polarity affects airway drug concentration and systemic drug absorption and to determine the effect of inhaled statins on naïve airway immune cell populations and alveolar-capillary membrane and epithelial barrier integrity in healthy rhesus monkeys. In this particular component of the study, we investigated the metabolic effects resulting from the use of statins in these healthy rhesus monkeys. Specifically, the Newman lab analyzed for lipid mediator (oxylipin, endocannabinoid, fatty acid, and nitro lipid) in lung and trachea tissue, plasma, and BAL and bile acid changes in the lung and trachea tissue and plasma.
Targeting Myelin NEFA of Kallikrein 6 Signals through PAR1 and PAR2 to Enchance Recovery of Function after SCI
STUDY_SUMMARY
Targeting mouse myelin NEFA of Kallikrein 6 Signals through PAR1 and PAR2 to Enchance Recovery of Function after SCI. The samples submitted are purified myelin preparations from the postnatal day 21, 60, or 90 mouse spinal cord (SC). There are 9 samples total in Project 1, n=3 for each genotype (control, PAR1 or PAR2) at 21 days. There are 9 samples total in Project 2, n=3 for each genotype (WT, PAR1-/- or PAR2-/-) at 60 days. There are 12 samples total in Project 3, n=3 for K6+/+ or K6-/- at either P21 or P90.
INSTITUTE
Mayo Clinic
LAST_NAME
Scarisbrick
FIRST_NAME
Isobel
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Targeting Myelin FFA Compostion of Kallikrein 6 Signals through PAR1 and PAR2 to Enchance Recovery of Function after SCI
STUDY_SUMMARY
Targeting mouse myelin FFA composition of Kallikrein 6 Signals through PAR1 and PAR2 to Enchance Recovery of Function after SCI. The samples submitted are purified myelin preparations from the postnatal day 21, 60, or 90 mouse spinal cord (SC). There are 9 samples total in Project 1, n=3 for each genotype (control, PAR1 or PAR2) at 21 days. There are 9 samples total in Project 2, n=3 for each genotype (WT, PAR1-/- or PAR2-/-) at 60 days. There are 12 samples total in Project 3, n=3 for K6+/+ or K6-/- at either P21 or P90.
INSTITUTE
Mayo Clinic
LAST_NAME
Scarisbrick
FIRST_NAME
Isobel
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Targeting Myelin Cholesterol of Kallikrein 6 Signals through PAR1 and PAR2 to Enchance Recovery of Function after SCI
STUDY_SUMMARY
Targeting mouse myelin Cholesterol of Kallikrein 6 Signals through PAR1 and PAR2 to Enchance Recovery of Function after SCI. The samples submitted are purified myelin preparations from the postnatal day 21, 60, or 90 mouse spinal cord (SC). There are 9 samples total in Project 1, n=3 for each genotype (control, PAR1 or PAR2) at 21 days. There are 9 samples total in Project 2, n=3 for each genotype (WT, PAR1-/- or PAR2-/-) at 60 days. There are 12 samples total in Project 3, n=3 for K6+/+ or K6-/- at either P21 or P90.
INSTITUTE
Mayo Clinic
LAST_NAME
Scarisbrick
FIRST_NAME
Isobel
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Targeting Myelin Sphingolipids of Kallikrein 6 Signals through PAR1 and PAR2 to Enchance Recovery of Function after SCI
STUDY_SUMMARY
Targeting Myelin Sphingolipids of Kallikrein 6 Signals through PAR1 and PAR2 to Enchance Recovery of Function after SCI. The samples submitted are purified myelin preparations from the postnatal day 21, 60, or 90 mouse spinal cord (SC). There are 9 samples total in Project 1, n=3 for each genotype (control, PAR1 or PAR2) at 21 days. There are 9 samples total in Project 2, n=3 for each genotype (WT, PAR1-/- or PAR2-/-) at 60 days. There are 12 samples total in Project 3, n=3 for K6+/+ or K6-/- at either P21 or P90.
INSTITUTE
Mayo Clinic
LAST_NAME
Scarisbrick
FIRST_NAME
Isobel
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Targeting Myelin Galactosyl Sphingolipids of Kallikrein 6 Signals through PAR1 and PAR2 to Enchance Recovery of Function after SCI
STUDY_SUMMARY
Targeting mouse myelin Galactosyl Shingolipids of Kallikrein 6 Signals through PAR1 and PAR2 to Enchance Recovery of Function after SCI. The samples submitted are purified myelin preparations from the postnatal day 21, 60, or 90 mouse spinal cord (SC). There are 9 samples total in Project 1, n=3 for each genotype (control, PAR1 or PAR2) at 21 days. There are 9 samples total in Project 2, n=3 for each genotype (WT, PAR1-/- or PAR2-/-) at 60 days. There are 12 samples total in Project 3, n=3 for K6+/+ or K6-/- at either P21 or P90.
INSTITUTE
Mayo Clinic
LAST_NAME
Scarisbrick
FIRST_NAME
Isobel
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Targeting Myelin Sphinomyelin concentrations of Kallikrein 6 Signals through PAR1 and PAR2 to Enchance Recovery of Function after SCI
STUDY_SUMMARY
Targeting Mouse Myelin Sphingomyelin concentrations of Kallikrein 6 Signals through PAR1 and PAR2 to Enchance Recovery of Function after SCI. The samples submitted are purified myelin preparations from the postnatal day 21, 60, or 90 mouse spinal cord (SC). There are 9 samples total in Project 1, n=3 for each genotype (control, PAR1 or PAR2) at 21 days. There are 9 samples total in Project 2, n=3 for each genotype (WT, PAR1-/- or PAR2-/-) at 60 days. There are 12 samples total in Project 3, n=3 for K6+/+ or K6-/- at either P21 or P90.
Targeted FFA Composition in Kallikrein 6 Mice after SCI
STUDY_SUMMARY
Targeted FFA Composition in Kallikrein 6 Mice after SCI. The samples submitted are purified myelin preparations from the postnatal day 21, 60, or 90 mouse spinal cord (SC). There are 12 samples total in Project 3, n=3 for K6+/+ or K6-/- at either P21 or P90.
Targeted NEFA in Kallikrein 6 Mice after SCI. The samples submitted are purified myelin preparations from the postnatal day 21, 60, or 90 mouse spinal cord (SC). There are 12 samples total in Project 3, n=3 for K6+/+ or K6-/- at either P21 or P90.
Targeted Cholesterol Profiling of Myelin to Enhance Recovery of Function after SCI. Second Set of Samples
STUDY_SUMMARY
Tissue is from adult mouse spinal cord (SC). We are submitting these samples for Untargeted Profiling (unbiased metabolomics assay) and for lipid analysis. The lipid assays we request are 1) free fatty acid composition of lipids; 2) free fatty acid panel; 3) cholesterol concentration (free and bound); 4) Ceramides, including galactosyl and glucosyl; 5) sphingomyelin. The Untargeted profiling is our top priority, followed by the lipid assays as listed. All samples were snap frozen at the point of harvest and approximate weights are provided. The samples are submitted as intact pieces of tissue. There are 20 samples total, n=5 for each group that includes LF (low fat diet); HF (high fat diet); HFHS (high fat high sucrose diet); and Keto (ketogenic diet).
Targeted Sphingolipids in Kallikrein 6 Mice after SCI
STUDY_SUMMARY
Targeted Sphingolipids in Kallikrein 6 Mice after SCI. The samples submitted are purified myelin preparations from the postnatal day 21, 60, or 90 mouse spinal cord (SC). There are 12 samples total in Project 3, n=3 for K6+/+ or K6-/- at either P21 or P90.
Targeted Galactosyl Sphingolipid Concentration in Kallikrein 6 Mice after SCI
STUDY_SUMMARY
Targeted Galactosyl Sphingolipids in Kallikrein 6 Mice after SCI. The samples submitted are purified myelin preparations from the postnatal day 21, 60, or 90 mouse spinal cord (SC). There are 12 samples total in Project 3, n=3 for K6+/+ or K6-/- at either P21 or P90.
Targeted Sphingomyelin Concentrations in Kallikrein 6 Mice after SCI
STUDY_SUMMARY
Targeted Sphingomyelin in Kallikrein 6 Mice after SCI. The samples submitted are purified myelin preparations from the postnatal day 21, 60, or 90 mouse spinal cord (SC). There are 12 samples total in Project 3, n=3 for K6+/+ or K6-/- at either P21 or P90.
Targeting Myelin NEFA in PAR1 and PAR2 Mice after SCI
STUDY_SUMMARY
Targeting Myelin NEFA in PAR1 and PAR2 Mice after SCI. The samples submitted are purified myelin preparations from the postnatal day 21 or 60 mouse spinal cord (SC). There are 30 total sampes, n=5 for each group. wild type control, PAR1 KO and PAR2 KO at P21 and P60 days.
Targeting Myelin FFA Compostion in PAR1 and PAR2 Mice after SCI
STUDY_SUMMARY
Targeting Myelin FFA composition in PAR1 and PAR2 Mice after SCI. The samples submitted are purified myelin preparations from the postnatal day 21 or 60 mouse spinal cord (SC). There are 30 total sampes, n=5 for each group. wild type control, PAR1 KO and PAR2 KO at P21 and P60 days.
Targeting Myelin Cholesterol in PAR1 and PAR2 Mice after SCI
STUDY_SUMMARY
Targeting Myelin Cholesterol in PAR1 and PAR2 Mice after SCI. The samples submitted are purified myelin preparations from the postnatal day 21 or 60 mouse spinal cord (SC). There are 30 total sampes, n=5 for each group. wild type control, PAR1 KO and PAR2 KO at P21 and P60 days.
Targeting Myelin Ceramides in PAR1 and PAR2 Mice after SCI
STUDY_SUMMARY
Targeting Myelin ceramides in PAR1 and PAR2 Mice after SCI. The samples submitted are purified myelin preparations from the postnatal day 21 or 60 mouse spinal cord (SC). There are 30 total sampes, n=5 for each group. wild type control, PAR1 KO and PAR2 KO at P21 and P60 days.
Identification of Race-Associated Metabolite Biomarkers for Hepatocellular Carcinoma
STUDY_SUMMARY
Introduction: Metabolomics provides simultaneous assessment of a broad range of metabolites that can potentially serve as indicators of the overall physiology status as well as the response to host and environmental stimuli. It has been broadly used for biomarker discovery and characterization of complex diseases such as cancer. The evaluation of the changes in the levels of metabolites in samples stratified by race could lead to the identification of more reliable biomarkers than those obtained through whole-population-based approaches. In this study, we used plasma samples collected from patients recruited at MedStar Georgetown University Hospital to investigate metabolites that may be associated with hepatocellular carcinoma (HCC) in a race-specific manner. Methods: Plasma samples were protein depleted using a solution composed of acetonitrile:isopropanol:water (3:3:2) containing a mixture of isotope-labeled internal standards. The extracted metabolites were trimethylsilyl derivatized prior to analysis by GC-MS. A quality control (QC) sample derived by pooling plasma from multiple subjects was run in between samples to assess reproducibility. A mixture of fatty acids methyl esters (FAMEs) and alkane standards was run for retention index calibration. The mixture of isotope-labeled internal standards was used to evaluate the reproducibility of the GC-MS data across multiple runs. Preliminary Data: Plasma samples collected from 40 HCC cases and 44 patients with liver cirrhosis were analyzed. The cirrhotic controls were frequency matched with the HCC cases by demographic variables. The participants included 19 African Americans (AA) and 50 European Americans (EA). The analysis targeted 46 metabolites for quantitative analysis by Agilent GC-qMS in selected ion monitoring (SIM) mode. The data were pre-processed by the Automated Mass Spectral Deconvolution and Identification System (AMDIS) for peak detection, deconvolution, and identification. The resulting peaks were aligned using Mass Profiler Professional (MPP) from Agilent Technologies. A LASSO regression model was applied to select metabolites with significant changes in HCC vs. cirrhosis in three groups: (1) AA and EA combined; (2) AA only; and (3) EA only. Also, metabolites that distinguish HCC cases from cirrhosis in the three groups were selected by considering only those subjects with Hepatitis C virus (HCV) infection. The performances of the metabolites selected by LASSO in each group were evaluated through a leave-one-out cross-validation. We identified race-specific metabolites that differentiated HCC cases from cirrhotic controls, yielding better area under the ROC curve compared to alpha-fetoprotein (AFP) - the serological marker widely used for the diagnosis of HCC. Novel Aspect: We identified race-associated metabolites that are significantly altered in HCC vs. cirrhosis, suggesting the potential role of race in HCC.
INSTITUTE
Georgetown University
DEPARTMENT
Oncology, Georgetown University Medical Center
LABORATORY
Ressom Lab (PI: Habtom W. Ressom, email address hwr@georgetown.edu)
LAST_NAME
Cristina
FIRST_NAME
Di Poto
ADDRESS
3970 Reservoir Rd., NW, Research Bldg, Room W325, Washington, DC, 20007, USA
Large Untargeted Profiling in PAR1 and PAR2 Mice after SCI
STUDY_SUMMARY
Large Untargeted Profiling in NEFA in PAR1 and PAR2 Mice after SCI. The samples submitted are purified myelin preparations from the postnatal day 21 or 60 mouse spinal cord (SC). There are 30 total sampes, n=5 for each group. wild type control, PAR1 KO and PAR2 KO at P21 and P60 days.
In this study, two independent large cohorts of mature dates exhibiting substantial diversity in origin, varieties and fruit processing conditions were measured by metabolomics techniques in order to identify major determinants of the fruit metabotype. Additional samples reflecting different stages of date fruit ripening process has been included for 10 different fruit varieties. This study includes updated date photographs and combined results data (GCMS/LCMS) and technical validation data, see downloadable files section to access this information.
Large Untargeted Profiling in Kallikrein 6 Mice after SCI
STUDY_SUMMARY
Large untargeted profiling mouse myelin of Kallikrein 6 Signals through PAR1 and PAR2 to Enchance Recovery of Function after SCI. The samples submitted are purified myelin preparations from the postnatal day 21, 60, or 90 mouse spinal cord (SC). There are 12 samples total in Project 3, n=3 for K6+/+ or K6-/- at either P21 or P90.
Metabolomic investigations on Nesterenkonia flava from different origins revealed significant intraspecies differences between marine and terrestrial actinomycetes
STUDY_SUMMARY
Marine is one of the most important resources of microorganisms, including bacteria, actinomycetes, and fungi. As marine and terrestrial environments differ a lot in many aspects it is not surprising that the species and characteristics of microorganisms living there are very different. Interestingly, many marine microorganisms can find their congeners of the same species from terrestrial resources. The aim of this work is to evaluate the intraspecies differences between marine and terrestrial actinomycetes on metabolic level and to uncover the mechanism responsible for the differences. To address this, we carried out comparative metabolomics study on Nesterenkonia flava strains isolated from marine and terrestrial environments. The results showed that marine strains were clearly distinguished from their terrestrial congeners on the principal components analysis (PCA) scores plot of intracellular metabolites. The markers responsible for the discrimination of marine and terrestrial strains were figured out using loading plot from partial least squares discrimination analysis (PLS-DA). Pathway analysis based on PLS-DA, univariate analysis, and correlation analysis of metabolites showed that the major differential metabolites between the terrestrial N. flava and the marine ones were involved in osmotic regulation, redox balancing, and energy metabolism. Together, these insights provide clues as to how the previous living environment of microbes affect their current metabolic performances under laboratory cultivation conditions.
INSTITUTE
Third Institute of Oceanography, State Oceanic Administration
Micronutrient deficiencies, environmental exposures and severe malaria: Risk factors for adverse neurodevelopmental outcomes in Ugandan children
STUDY_TYPE
Untargeted high-resolution mass spectrometry profiling
STUDY_SUMMARY
Micronutrient deficiencies and environmental exposures have been to known to adversely impact brain and nervous system functions in adults and children worldwide. However, few studies have examined the short and long-term impact of these risk factors on neurodevelopmental outcomes in children in low-income countries, where the effects are likely to be more pronounced due to limited resources for monitoring and insufficient regulations. Biological risk factors of relevance include micronutrient deficiencies such as zinc and exposure to heavy metals such as lead and mercury. Studies have suggested an association between neurodevelopmental impairment and micronutrient deficiency as well as exposure to a number of heavy metals and environmental toxins. Moreover, findings also suggest that risk factors for adverse developmental outcomes that are independently significant may have the potential for causing cumulative increases in adverse effects. In Sub-Saharan Africa, severe malaria is a leading risk factor for long-term neurocognitive impairment in children. Zinc deficiency or exposure to heavy metals could influence risk of severe malaria, modify the risk of neurocognitive impairment in children with severe malaria, or independently affect risk of neurocognitive impairment. Untargeted analyses for potential environmental exposures or metabolomic changes in children with cerebral malaria vs. without cognitive impairment or in children with higher vs. lower cognitive scores, could also identify new risk factors for neurodevelopmental impairment in Ugandan children with cerebral malaria.In our completed study in Kampala, we assessed neurologic and developmental impairment in children with cerebral malaria [CM] or severe malarial anemia [SMA], as compared to health community children from the same extended household as the children with CM or SMA. As an extension of this study, we are interested in determining levels of micronutrients such as zinc in the population, and in addition, determining exposure levels of heavy metals (lead, mercury, copper, manganese etc.) in samples collected from children with severe malaria and community controls. The primary hypotheses of this study is that nutrient deficiencies or exposure to heavy metals influence short and long term neurocognitive outcomes in healthy community children and in children with severe malaria, and that children with cerebral malaria have specific metabolomic changes that relate to long-term neurocognitive impairment. The specific aims of our study are:Aim 1: To determine levels of zinc, heavy metals, and biomarkers associated with inflammation in children presenting with different forms of severe malaria (SM) and in healthy community children (CC). The working hypothesis of this aim is that 1) children with SM will have lower zinc levels compared to CC; 2) children with SM will present with higher toxic metal exposure and higher levels of biomarkers associated with inflammation than CC.Aim 2: To investigate how micronutrient deficiency, toxic metal exposure and inflammatory biomarkers affect short and long term neurodevelopmental outcomes and growth in children with severe malaria and community children (CC).The working hypothesis of this aim is that the lower levels of zinc, and presence of toxic metals in high concentrations will independently contribute to worsening neurodevelopmental outcomes and worsening growth over time in children with severe malaria and in community children. An alternate hypothesis is that micronutrient deficiency, toxic metal exposure and inflammatory states may interact with each other and with severe malaria to produce greater neurodevelopmental impairment, i.e., that the contribution is not independent but interactive.Aim 3: To determine whether the CSF metabolome differs according to level of neurodevelopmental impairment in children with cerebral malaria. The working hypothesis of this aim is that neurodevelopmental impairment in children with cerebral malaria is associated with changes in the CSF metabolome.
INSTITUTE
Emory University School of Medicine
DEPARTMENT
Division of Pulmonary, Allergy and Critical Care Medicine
LABORATORY
Clincal Biomarkers Laboratory
LAST_NAME
Walker
FIRST_NAME
Douglas
ADDRESS
615 Michael St. Ste 225, Atlanta, GA, 30322, USA
EMAIL
douglas.walker@emory.edu
PHONE
(404) 727 5984
TOTAL_SUBJECTS
141
STUDY_COMMENTS
CSF pools from elderly individuals included for QA/QC. Study specific pools were not created due to limited sample volumes provided (<100uL).
Evidence that COG0325 proteins are involved in PLP homeostasis
STUDY_SUMMARY
Pyridoxal 5'-phosphate (PLP) is an essential cofactor for nearly 60 Escherichia coli enzymes but is a highly reactive molecule that is toxic in its free form. How PLP levels are regulated and how PLP is delivered to target enzymes are still open questions. The COG0325 protein family belongs to the fold-type III class of PLP enzymes and binds PLP but has no known biochemical activity although it occurs in all kingdoms of life. Various pleiotropic phenotypes of the E. coli COG0325 (yggS) mutant have been reported, some of which were reproduced and extended in this study. Comparative genomic, genetic and metabolic analyses suggest that these phenotypes reflect an imbalance in PLP homeostasis. The E. coli yggS mutant accumulates the PLP precursor pyridoxine 5'-phosphate (PNP) and is sensitive to an excess of pyridoxine but not of pyridoxal. The pyridoxine toxicity phenotype is complemented by the expression of eukaryotic yggS orthologs. It is also suppressed by the presence of amino acids, specifically isoleucine, threonine and leucine, suggesting the PLP-dependent enzyme transaminase B (IlvE) is affected. These genetic results lay a foundation for future biochemical studies of the role of COG0325 proteins in PLP homeostasis.
INSTITUTE
University of California, Davis
DEPARTMENT
Genome and Biomedical Sciences Facility
LABORATORY
WCMC Metabolomics Core
LAST_NAME
Fiehn
FIRST_NAME
Oliver
ADDRESS
1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
EMAIL
ofiehn@ucdavis.edu
PHONE
(530) 754-8258
STUDY_COMMENTS
LB stands for Luria Bertani medium. MG stands for minimal growth For strains grown on MG OD 0.5 is the mid log growth phase and OD 1.0 is the late log growth phase For strains grown on LB OD 1 is the mid log growth phase and OD 2.0 is the late log growth phase
Mechanism Behind Stay Green Trait in Bread Wheat (Triticum aestivum L.)
STUDY_TYPE
Comparison
STUDY_SUMMARY
Two different wheat genotypes were treated with the high temperature and control conditions under full irrigated condition. Leaf tissues were collected for all 2-different treatments with six replicates after 7 and 10 days of high temperature treatment.
Free fatty acids in mouse plasma were identified and quantified by LC-MS. Through differential feeding and PHZ (phnylhydrazine) dosing, coupled with mass spectrometry, we identified the long chain fatty acid C24:5 as a natural RXRA ligand, which was dynamically increased in concentration in response to hematopoietic stress. Collectively, these data demonstrate that natural RXRA ligands are present and are dynamically regulated in vivo in mouse hematopoietic cells.
NMR comparison of urine samples by 1D NOESY presat and PURGE
STUDY_TYPE
NMR development for metabolomics
STUDY_SUMMARY
Different water suppression pulse sequences, namely 1D NOESY presat and optimized PURGE were compared for urine samples. The original PURGE sequence was also tested to show the postential for lineshape distortions with the pulse sequence.
Comparison of T2 filters for quantification of small molecules in plasma by 1D NMR
STUDY_TYPE
NMR development for metabolomics
STUDY_SUMMARY
A pooled plasma sample obtained from Red Cross has been seperated into 20 samples. 10 of them were simply mixed with a D2O phosphate buffer, while the other 10 were centrifuged first, then dried and resuspended in a 90/10 H2O/D2O phosphate buffer. The 20 NMR samples were analysed by NMR (4 spectra per sample, but different pulse sequences and parameters were used for each group). Standard addition was used in order to measure the concentration of 5 metabolites: valine, lactate, glucose, phenylalanine and formate.
Murine vitamin A deficiency results in a hypermetabolic state and alterations in bacterial community structure and metabolism. (Liver)
STUDY_SUMMARY
Vitamin A deficiency (A-) is a significant public health problem. To better understand how vitamin A status influences gut microbiota and host metabolism, we systematically analyzed urine, cecum, serum, and liver samples from vitamin A sufficient (A+) and A- mice using 1H NMR-based metabolomics, quantitative (q)PCR, and 16S rRNA gene sequencing coupled with multivariate data analysis. The microbiota in the cecum of A- mice showed compositional as well as functional shifts compared to the microbiota from A+ mice. Targeted 1H NMR analyses revealed significant changes in microbial metabolite concentrations including higher butyrate and hippurate and decreased acetate and 4-hydroxyphenylacetate in A+ relative to A- mice. Bacterial butyrate-producing genes including butyryl-CoA:acetate CoA-transferase and butyrate kinase were significantly higher in bacteria from A+ versus bacteria from A- mice. A - mice had disturbances in multiple metabolic pathways including alterations in energy metabolism (hyperglycemia, glycogenesis, TCA cycle, and lipoprotein biosynthesis) and the A- host showed metabolites indicative of a hypermetabolic state (higher levels of amino acids and nucleic acids). A- mice had hyperglycemia, liver dysfunction, changes in bacterial metabolism, and altered gut microbial communities. Moreover, integrative analyses indicated a strong correlation between gut microbiota and host energy metabolism pathways in the liver. Vitamin A regulates the microbiota, bacterial metabolism and the effects of vitamin A on the microbiota results in alterations to host metabolism.
INSTITUTE
Pennsylvania State University
LAST_NAME
Nichols
FIRST_NAME
Robert
ADDRESS
101 Life science building, University park, PA, 16803
Murine vitamin A deficiency results in a hypermetabolic state and alterations in bacterial community structure and metabolism. (Serum)
STUDY_SUMMARY
Vitamin A deficiency (A-) is a significant public health problem. To better understand how vitamin A status influences gut microbiota and host metabolism, we systematically analyzed urine, cecum, serum, and liver samples from vitamin A sufficient (A+) and A- mice using 1H NMR-based metabolomics, quantitative (q)PCR, and 16S rRNA gene sequencing coupled with multivariate data analysis. The microbiota in the cecum of A- mice showed compositional as well as functional shifts compared to the microbiota from A+ mice. Targeted 1H NMR analyses revealed significant changes in microbial metabolite concentrations including higher butyrate and hippurate and decreased acetate and 4-hydroxyphenylacetate in A+ relative to A- mice. Bacterial butyrate-producing genes including butyryl-CoA:acetate CoA-transferase and butyrate kinase were significantly higher in bacteria from A+ versus bacteria from A- mice. A - mice had disturbances in multiple metabolic pathways including alterations in energy metabolism (hyperglycemia, glycogenesis, TCA cycle, and lipoprotein biosynthesis) and the A- host showed metabolites indicative of a hypermetabolic state (higher levels of amino acids and nucleic acids). A- mice had hyperglycemia, liver dysfunction, changes in bacterial metabolism, and altered gut microbial communities. Moreover, integrative analyses indicated a strong correlation between gut microbiota and host energy metabolism pathways in the liver. Vitamin A regulates the microbiota, bacterial metabolism and the effects of vitamin A on the microbiota results in alterations to host metabolism.
INSTITUTE
Pennsylvania State University
LAST_NAME
Nichols
FIRST_NAME
Robert
ADDRESS
101 Life science building, University park, PA, 16803
Murine vitamin A deficiency results in a hypermetabolic state and alterations in bacterial community structure and metabolism.(Urine)
STUDY_SUMMARY
Vitamin A deficiency (A-) is a significant public health problem. To better understand how vitamin A status influences gut microbiota and host metabolism, we systematically analyzed urine, cecum, serum, and liver samples from vitamin A sufficient (A+) and A- mice using 1H NMR-based metabolomics, quantitative (q)PCR, and 16S rRNA gene sequencing coupled with multivariate data analysis. The microbiota in the cecum of A- mice showed compositional as well as functional shifts compared to the microbiota from A+ mice. Targeted 1H NMR analyses revealed significant changes in microbial metabolite concentrations including higher butyrate and hippurate and decreased acetate and 4-hydroxyphenylacetate in A+ relative to A- mice. Bacterial butyrate-producing genes including butyryl-CoA:acetate CoA-transferase and butyrate kinase were significantly higher in bacteria from A+ versus bacteria from A- mice. A - mice had disturbances in multiple metabolic pathways including alterations in energy metabolism (hyperglycemia, glycogenesis, TCA cycle, and lipoprotein biosynthesis) and the A- host showed metabolites indicative of a hypermetabolic state (higher levels of amino acids and nucleic acids). A- mice had hyperglycemia, liver dysfunction, changes in bacterial metabolism, and altered gut microbial communities. Moreover, integrative analyses indicated a strong correlation between gut microbiota and host energy metabolism pathways in the liver. Vitamin A regulates the microbiota, bacterial metabolism and the effects of vitamin A on the microbiota results in alterations to host metabolism.
INSTITUTE
Pennsylvania State University
LAST_NAME
Nichols
FIRST_NAME
Robert
ADDRESS
101 Life science building, University park, PA, 16803
Murine vitamin A deficiency results in a hypermetabolic state and alterations in bacterial community structure and metabolism. (Cecal contents)
STUDY_SUMMARY
Vitamin A deficiency (A-) is a significant public health problem. To better understand how vitamin A status influences gut microbiota and host metabolism, we systematically analyzed urine, cecum, serum, and liver samples from vitamin A sufficient (A+) and A- mice using 1H NMR-based metabolomics, quantitative (q)PCR, and 16S rRNA gene sequencing coupled with multivariate data analysis. The microbiota in the cecum of A- mice showed compositional as well as functional shifts compared to the microbiota from A+ mice. Targeted 1H NMR analyses revealed significant changes in microbial metabolite concentrations including higher butyrate and hippurate and decreased acetate and 4-hydroxyphenylacetate in A+ relative to A- mice. Bacterial butyrate-producing genes including butyryl-CoA:acetate CoA-transferase and butyrate kinase were significantly higher in bacteria from A+ versus bacteria from A- mice. A - mice had disturbances in multiple metabolic pathways including alterations in energy metabolism (hyperglycemia, glycogenesis, TCA cycle, and lipoprotein biosynthesis) and the A- host showed metabolites indicative of a hypermetabolic state (higher levels of amino acids and nucleic acids). A- mice had hyperglycemia, liver dysfunction, changes in bacterial metabolism, and altered gut microbial communities. Moreover, integrative analyses indicated a strong correlation between gut microbiota and host energy metabolism pathways in the liver. Vitamin A regulates the microbiota, bacterial metabolism and the effects of vitamin A on the microbiota results in alterations to host metabolism.
INSTITUTE
Pennsylvania State University
LAST_NAME
Nichols
FIRST_NAME
Robert
ADDRESS
101 Life science building, University park, PA, 16803
Metabolomics Linking Air Pollution, Obesity and Type 2 Diabetes
STUDY_TYPE
Untargeted high-resolution mass spectrometry profiling
STUDY_SUMMARY
The overall goal of this proposal is to use blood non-targeted high resolution metabolomics (HRM) to investigate the hypothesis that regional air pollution (NO2, PM2.5 and O3) and traffic-related air pollution exposures (traffic-related particulate matter components including EC2.5 and PM2.5 transition metals, and CALINE model-predicted NOx) alter key metabolic pathway(s) and that these alterations are associated with obesity and type 2 diabetes-related traits during the important developmental period of adolesence in the ongoing prospective Chidlren's Health study (CHS). Specific Aim 1 will examine the adverse impact of environmental chemicals in fasting blood samples measured by HRM on obesity (i.e., total body fat and body mass index (BMI)), metabolic dysfunction (e.g., fasting glucose and insulin concentrations and insulin resistance), and obesity-induced inflammation (i.e., leptin) among 104 Southern California adolescents enrolled in the CHS. Specific Aim 2 will examine associations of childhood exposures to PM2.5 and traffic-related air pollutants (i.e., CALINE model-predicted NOx) with biological metabolites identified in fasting blood samples using HRM among 104 adolescents in the CHS. Specific Aim 3 will investigate the metabolic pathways linking air pollution exposures and obesity and type 2 diabetes-related traits using pathway analysis under bayesian hierarchical model among 104 adolescents in the CHS.
INSTITUTE
Emory University School of Medicine
DEPARTMENT
Division of Pulmonary, Allergy and Critical Care Medicine
LABORATORY
Clincal Biomarkers Laboratory
LAST_NAME
Walker
FIRST_NAME
Douglas
ADDRESS
615 Michael St. Ste 225, Atlanta, GA, 30322, USA
EMAIL
douglas.walker@emory.edu
PHONE
(404) 727 5984
TOTAL_SUBJECTS
104
STUDY_COMMENTS
Both CHEAR and Clinical Biomarker Laboratory pooled plasma samples were used for quality control. Study specific sample pools were not created
Metabolomic adaptation of a deep sea Microbacterium sediminis to prolonged low temperature under high pressure
STUDY_SUMMARY
Low temperature is the most wide-spread “hostile” environmental factor on earth while at the same time the most common condition for marine organisms. However, the unique adaptive mechanisms that enable the survival of marine microorganisms under low temperature are unclear. Since low temperature is always accompanied by high pressure and other adverse conditions in marine environment, here we studied the metabolic adaptation of a marine strain to prolonged low temperature under high pressure. The strain studied is a psychrotolerant Microbacterium sediminis isolated from deep sea sediment. By using 1H nuclear magnetic resonance (NMR)-based metabolomics approach, we detected the spectral data of polar extracts of the strain M. sediminis, and applied multivariate statistical analysis methods together with univariate analysis to analyze metabolic profiles associated to different conditions. The metabolic profiles of the M. sediminis strain cultivated under high pressure at low temperature were distinctly different from those cultivated under high pressure at normal temperature. We identified the differential metabolites which were responsible for distinguishing the metabolic profiles and compared their relative intensities between groups. We also compared the different adaptive responses of the strain at different growth stages to the prolonged low temperature under high pressure. We proposed that the low-temperature adapting process of the M. sediminis strain involves, 1) the regulation of osmotic pressure using amino acids as possible alternative osmolytes, and, 2) the strengthen of glycolysis and the maintenance of TCA cycle via amino acids anaplerotic reaction. We put forward that the main difference of adaptation to low temperature for the strain at different growth stages was related to energy metabolism. Our findings improved the understanding of the low-temperature adaptive mechanisms for marine microorganisms under high pressure on the metabolic level.
INSTITUTE
Third Institute of Oceanography, State Oceanic Administration
Biomarkers of NAFLD progression: a lipidomics approach to an epidemic. Part 1:Liver
STUDY_TYPE
Lipidomics Study
STUDY_SUMMARY
The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely diagnosis of these different stages, particularly NASH, is important for both potential reversibility and limitation of complications. Liver biopsy remains the clinical standard for definitive diagnosis. Diagnostic tools minimizing the need for invasive procedures or that add information to histologic data are important in novel management strategies for the growing epidemic of NAFLD. We describe an 'omics' approach to detecting a reproducible signature of lipid metabolites, aqueous intracellular metabolites, SNPs, and mRNA transcripts in a double-blinded study of patients with different stages of NAFLD that involves profiling liver biopsies, plasma, and urine samples. Using linear discriminant analysis, a panel of 20 plasma metabolites that includes glycerophospholipids, sphingolipids, sterols, and various aqueous small molecular weight components involved in cellular metabolic pathways, can be used to differentiate between NASH and steatosis. This identification of differential biomolecular signatures has the potential to improve clinical diagnosis and facilitate therapeutic intervention of NAFLD.
Biomarkers of NAFLD progression: a lipidomics approach to an epidemic. Part 1:Plasma
STUDY_TYPE
Lipidomics Study
STUDY_SUMMARY
The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely diagnosis of these different stages, particularly NASH, is important for both potential reversibility and limitation of complications. Liver biopsy remains the clinical standard for definitive diagnosis. Diagnostic tools minimizing the need for invasive procedures or that add information to histologic data are important in novel management strategies for the growing epidemic of NAFLD. We describe an 'omics' approach to detecting a reproducible signature of lipid metabolites, aqueous intracellular metabolites, SNPs, and mRNA transcripts in a double-blinded study of patients with different stages of NAFLD that involves profiling liver biopsies, plasma, and urine samples. Using linear discriminant analysis, a panel of 20 plasma metabolites that includes glycerophospholipids, sphingolipids, sterols, and various aqueous small molecular weight components involved in cellular metabolic pathways, can be used to differentiate between NASH and steatosis. This identification of differential biomolecular signatures has the potential to improve clinical diagnosis and facilitate therapeutic intervention of NAFLD.
Biomarkers of NAFLD progression: a lipidomics approach to an epidemic. Part 3:Urine
STUDY_TYPE
Lipidomics Study
STUDY_SUMMARY
The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely diagnosis of these different stages, particularly NASH, is important for both potential reversibility and limitation of complications. Liver biopsy remains the clinical standard for definitive diagnosis. Diagnostic tools minimizing the need for invasive procedures or that add information to histologic data are important in novel management strategies for the growing epidemic of NAFLD. We describe an 'omics' approach to detecting a reproducible signature of lipid metabolites, aqueous intracellular metabolites, SNPs, and mRNA transcripts in a double-blinded study of patients with different stages of NAFLD that involves profiling liver biopsies, plasma, and urine samples. Using linear discriminant analysis, a panel of 20 plasma metabolites that includes glycerophospholipids, sphingolipids, sterols, and various aqueous small molecular weight components involved in cellular metabolic pathways, can be used to differentiate between NASH and steatosis. This identification of differential biomolecular signatures has the potential to improve clinical diagnosis and facilitate therapeutic intervention of NAFLD.
Metabolomics Analysis of Aqueous Humour in the Presence of Glaucoma Drainage Devices
STUDY_TYPE
Metabolomics Evaluation of Aqueous Humor Samples from Left (treated) and Right (Control) Eyes of Rabbits.
STUDY_SUMMARY
Metabolomic experiments were carried out on aqueous humor samples provided by Ramesh Ayyala. Through this collaboration, we propose to study aqueous humor from control and experimental rabbits to better understand metabolic differences in the aqueous humor samples.
Define alterations in the gut metabolome of mice infected with C. difficile
STUDY_TYPE
Time course experiment
STUDY_SUMMARY
C57BL/6 mice were treated with antibiotics to make them susceptible to C. difficile. Mice were challenged with C. difficile and the infection was monitored for 30 hours post challenge. Mice were sacrificed at 0 hr, 12 hr, 24 hr, and 30 hr post challenge with C. difficile and gut content was collected for untargeted metabolomic analysis. The aim of this project was to define the gut metabolome throughout C. difficile infection.
"Utilizing Ion Mobility Spectrometry and Mass Spectrometry for the Analysis of Polycyclic Aromatic Hydrocarbons, Polychlorinated Biphenyls, Polybrominated Diphenyl Ethers and Their Metabolites mass spectrometry"
STUDY_TYPE
Structural analysis of xenobiotics using ion mobility
STUDY_SUMMARY
Standards of xenobiotics were analyzed with Agilent 6560 Ion mobility QTOF MS platform to find Collision Cross Section values. All measurements were performed in triplicate in both positive and negative polarities with nitrogen gas and at seven different electric fields, so that values could be directly measured and random standard deviations (RSD) assessed for each molecule.
INSTITUTE
Pacific Northwest National Laboratory
DEPARTMENT
Integrative Omics
LABORATORY
Pacific Northwest National Laboratory
LAST_NAME
Baker
FIRST_NAME
Erin
ADDRESS
Pacific Northwest National Laboratory 902 Battelle Boulevard Richland, WA
Specific Aims: (a) Identify sex differences in serum untargeted metabolomics profiles during late adolescence, (b) examine changes in metabolomics profiles between early and late adolescence in the same children, and (c) evaluate associations of exposure to prenatal and concurrent exposure to PAHs, metals, and EDCs with serum metabolite profiles among boys and girls, separately, during late adolescence.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
EMAIL
mkachman@med.umich.edu
PHONE
(734) 232-8175
NUM_GROUPS
2
TOTAL_SUBJECTS
207
STUDY_COMMENTS
The overall objective of this project is to expand upon available data from Early Life Exposure in Mexico to ENvironental Toxicants (ELEMENT) Project to examine effects of toxicant exposures during three sensitive developmental timeframes – the prenatal period, early adolescence, and late adolescence – on adiposity and metabolic risk in adolescence with an emphasis on sex differences and the related molecular underpinnings. In addition to existing exposure data on BPA, metals and phthalates, we propose to add measures of polycyclic aromatic hydrocarbon (PAH) metabolites in archived urine samples from mothers and children. We also propose to assess the epigenome at three developmental periods (prenatal aka in utero, early and late adolescence) and the circulating metabolome during late adolescence. We will incorporate data on toxicant exposures and ‘omics, including untargeted metabolomics of 404 teenagers from the ELEMENT cohorts, to addressing several specific aims.
Mechanisms for Insulin Resistance in Polycystic Ovary Syndrome: aminoadipic acid, lysine concentrations, and enrichment (part I)
STUDY_SUMMARY
"To determine whether altered lysine and α-aminoadipic acid (AAA) kinetics explain previous observations of increased lysine and AAA concentrations in PCOS compared to controls, as measured by baseline lysine and AAA flux in PCOS versus healthy controls using [α-15N]-lysine and [13C]-AAA stable isotope tracers as well as by comparing the conversion of [α-15N]-lysine to [15N]-AAA. To evaluate how hyperinsulinemia affects lysine and AAA kinetics. Changes in lysine and AAA flux during a hyperinsulinemic-euglycemic clamp will be evaluated in healthy controls and compared to the baseline changes in lysine and AAA flux in PCOS."
INSTITUTE
Mayo Clinic
LAST_NAME
Chang
FIRST_NAME
Al
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Mechanisms for Insulin Resistance in Polycystic Ovary Syndrome: aminoadipic acid, lysine concentrations, and enrichment (part II)
STUDY_SUMMARY
"To determine how metformin therapy changes lysine and AAA kinetics in PCOS and whether this is associated with improvements in insulin sensitivity. Changes in lysine and AAA flux before and after three months of metformin therapy will be compared to women with PCOS randomized to no treatment for three months.
INSTITUTE
Mayo Clinic
LAST_NAME
Chang
FIRST_NAME
Alice
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Using Metabolomics and Lipidomics Analysis to Explore Metabolites and Pathways Associated Increased Airway Hyperresponsiveness in Patients with Asthma who are Identified by Race (African American) and Genotype (ADRB2 Arg16/Arg)
STUDY_TYPE
Open-label, prospective cohort study
STUDY_SUMMARY
Asthma is a heterogeneous disease largely defined by chronic airway inflammation with similar symptomatology in patients that includes wheezing, shortness of breath, chest tightness and cough. However, underlying these common symptoms are varying endotypes with distinct pathophysiological processes. Metabolomic studies in patients with asthma are emerging and suggest that metabolomics can characterize distinct asthma phenotypes. In a completed study, we identified a population of patients with asthma who have increased airway hyperresponsiveness (airway hyperresponsiveness is a marker for asthma disease severity) who are characterized by race (African American) and genotype (ADRB2 Arg16/Arg) compared with patients who have less airway hyperresponsiveness (African Americans and whites with differing ADRB2 genotypes). This group may represent a distinct endotype of asthma with unique metabolomic and lipidomic characteristics. The aims of this project are to (1) use metabolomic and lipidomic analysis to identify metabolites present in plasma in this population of patients with asthma who have increased airway hyperresponsiveness (African Americans who carry the ADRB2 Arg16/Arg genotype) and patients with asthma who have less airway hyperresponsiveness (African Americans and whites with differing ADRB2 genotypes); and (2) identify pathways that will improve the understanding of increased airway hyperresponsiveness in this population. We hypothesize that there will be unique metabolic pathways in the population with increased airway hyperresponsiveness that will be distinct from pathways in patients with lower airway hyperresponsiveness. In this project will use data and samples that were previously collected as part of the NIH funded project “Pharmacogenetics of β2-Agonists in Asthma” (Blake, PI K23 HL081245). Blood was collected in 55 African Americans and whites after receiving 2-weeks treatment with inhaled fluticasone. Samples were stored on ice until processed and plasma frozen at -80°C. If our findings indicate distinct metabolic pathways are present using global metabolomic and lipodomic analysis, we will seek to replicate our findings using samples and data from phenotypically well characterized participants who participated in trials conducted through the American Lung Association Airways Clinical Research Centers network, of which Nemours has been a highly productive site since 1999. Future controlled trials would be conducted to evaluate treatments based upon molecular pathways identified through metabolomic and lipidomic analysis.
INSTITUTE
University of Florida
DEPARTMENT
SECIM
LAST_NAME
Beecher
FIRST_NAME
Chris
ADDRESS
PO Box 100219 Gainesville FL 32610-0219 , Southeast Center for Integrated Metabolomics
EMAIL
chris@iroatech.com
PHONE
(352) 294-4385
NUM_GROUPS
4
TOTAL_SUBJECTS
55
STUDY_COMMENTS
Nubmer of groups : 4 (race x diplotype); SECIM pilot and feasibility, NIH U24 DK097209
The Influence of Sugar, Artificial Sweeteners, and the Microbiome on Rodent TCA Concentrations (part I)
STUDY_SUMMARY
Targeted TCA concentrations of rodents treated with diets rich in commonly used artifically sweeteners will be assessed in this study. We hypothesized that a specific subset of plasma metabolites are generated as a result from a diet rich in commonly used artificial sweeteners and their subsequent processing by the gut microbiome, which could ultimately lead to impaired glycemic control and negative physiological health outcomes. To test this hypothesis we administered normal, high glucose, fructose, aspartame, and acesulfame potassium diets to rats for 3 weeks, followed by a plasma collection through cardiac puncture and metabolic analysis. We also treated the gut microbiota with in rats with the same diets plus bacitracin/streptomycin to observe how alterations of the microbiome influence the plasma metabolic profile in these animals. The resulting data will give us insights into the influence of high sugar and artificial sweetener diets on homeostatic metabolic processes and dive into the symbiotic relationship of the gut microbiome with this process.
The Influence of Sugar, Artificial Sweeteners, and the Microbiome on Rodent Diacylglycerols (part II)
STUDY_SUMMARY
Targeted diacylglycerols panel of rodents treated with diets rich in commonly used artifically sweeteners will be assessed in this study. We hypothesized that a specific subset of plasma metabolites are generated as a result from a diet rich in commonly used artificial sweeteners and their subsequent processing by the gut microbiome, which could ultimately lead to impaired glycemic control and negative physiological health outcomes. To test this hypothesis we administered normal, high glucose, fructose, aspartame, and acesulfame potassium diets to rats for 3 weeks, followed by a plasma collection through cardiac puncture and metabolic analysis. We also treated the gut microbiota with in rats with the same diets plus bacitracin/streptomycin to observe how alterations of the microbiome influence the plasma metabolic profile in these animals. The resulting data will give us insights into the influence of high sugar and artificial sweetener diets on homeostatic metabolic processes and dive into the symbiotic relationship of the gut microbiome with this process.
The Influence of Sugar, Artificial Sweeteners, and the Microbiome on Rodent Triglyceride Composition (part III)
STUDY_SUMMARY
Targeted triglyceride concentration panel of rodents treated with diets rich in commonly used artifically sweeteners will be assessed in this study. We hypothesized that a specific subset of plasma metabolites are generated as a result from a diet rich in commonly used artificial sweeteners and their subsequent processing by the gut microbiome, which could ultimately lead to impaired glycemic control and negative physiological health outcomes. To test this hypothesis we administered normal, high glucose, fructose, aspartame, and acesulfame potassium diets to rats for 3 weeks, followed by a plasma collection through cardiac puncture and metabolic analysis. We also treated the gut microbiota with in rats with the same diets plus bacitracin/streptomycin to observe how alterations of the microbiome influence the plasma metabolic profile in these animals. The resulting data will give us insights into the influence of high sugar and artificial sweetener diets on homeostatic metabolic processes and dive into the symbiotic relationship of the gut microbiome with this process.
The Influence of Sugar, Artificial Sweeteners, and the Microbiome on Rodent Amino Acids (part IV)
STUDY_SUMMARY
Targeted Amino Acid panel of rodents treated with diets rich in commonly used artifically sweeteners will be assessed in this study. We hypothesized that a specific subset of plasma metabolites are generated as a result from a diet rich in commonly used artificial sweeteners and their subsequent processing by the gut microbiome, which could ultimately lead to impaired glycemic control and negative physiological health outcomes. To test this hypothesis we administered normal, high glucose, fructose, aspartame, and acesulfame potassium diets to rats for 3 weeks, followed by a plasma collection through cardiac puncture and metabolic analysis. We also treated the gut microbiota with in rats with the same diets plus bacitracin/streptomycin to observe how alterations of the microbiome influence the plasma metabolic profile in these animals. The resulting data will give us insights into the influence of high sugar and artificial sweetener diets on homeostatic metabolic processes and dive into the symbiotic relationship of the gut microbiome with this process.
Metabolite and gene expression profiles suggest a putative mechanism through which high dietary carbohydrates reduce the content of hepatic betaine in Megalobrama amblycephala
STUDY_SUMMARY
plasma of Megalobrama amblycephala fed with control diet, high carbohydrates diet,betaine diet with 16 weeks and betaine diet with 4 weeks.
INSTITUTE
College of Fisheries Huazhong Agricultural University
High Resolution GC-MS Metabolomics of Non-Human Primate Serum
STUDY_TYPE
Non-human Primate Serum
STUDY_SUMMARY
Rationale: Metabolomics analyses using gas chromatography mass spectrometry (GC-MS) - based metabolomics are heavily impeded by the lack of high-resolution mass spectrometers and limited spectral libraries to complement the excellent chromatography that GC platforms offer, a challenge that is being addressed with the implementation of high resolution (HR) platforms such as GC-Orbitrap-MS. Methods: We used serum samples from a non-human primate (NHP), a baboon (Papio hamadryas), with suitable quality controls to quantify the chemical space using an advanced HR MS platform for confident metabolite identification and robust quantification to assess the suitability of the platform for routine clinical metabolomics research. In a comparative approach, we also analyzed the same serum samples using a two-dimensional gas chromatography time-of-flight mass-spectrometer (2D GC-ToF-MS) for metabolite identification and quantification following established standard protocols. Results: Overall, the 2D GC-ToF-MS and GC-Orbitrap-MS analyses enabled identification and quantification of 555 total metabolites from the NHP serum with a spectral similarity score Rsim ≥ 900 and S/R ratio of > 25. A common set of 30 metabolites with HMDB and KEGG IDs were quantified in the serum samples by both platforms where the 2D GC-ToF-MS enabled quantification of a total 384 metabolites (118 HMDB IDs) and the GC-Orbitrap-MS analysis quantification of a total 200 metabolites (47 HMDB IDs). Conclusions: Our study provides insights into the benefits and limitations of the use of a higher mass accuracy instrument for untargeted GC-MS-based metabolomics with multi-dimensional chromatography in future studies addressing clinical conditions or exposome studies.
Metabolomic Markers of Dietary Patterns in the Costa Rica Study
STUDY_TYPE
MS analysis
STUDY_SUMMARY
The study will examine associations between dietary patterns and the metabolome on a random subset (n=80) of control subjects in a population-based case-control study of myocardial infarction in Costa Rican adults. Each sample will undergo complementary LC-MS-based approaches, specifically untargeted metabolite profiling and targeted lipidomic profiling. Subsequently we will test for associations between 1) previously derived dietary patterns and plasma molecular features and 2) the top plasma correlates of dietary patterns and metabolic syndrome.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Amino Acid Concentrations of Primary Sclerosing Cholangitis (part I)
STUDY_SUMMARY
To qualitatively and quantitatively analyze enterohepatically-circulated molecules using targeted amino acid concentrations of peripheral blood collected from primary sclerosing cholangitis (PSC) patients compared to normal and diseased controls. There are three groups of patients. (1) Normal donor controls (ND), (2) Patients with Primary Sclerosing Cholangitis (PSC), and (3) Disease Controls (DC) which are patients with liver disease other than PSC.
INSTITUTE
Mayo Clinic
LAST_NAME
O'Hara
FIRST_NAME
Steven
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Non-Esterified Fatty Acids of Primary Sclerosing Cholangitis (part II)
STUDY_SUMMARY
To qualitatively and quantitatively analyze enterohepatically-circulated molecules using targeted free fatty acid concentrations of peripheral blood collected from primary sclerosing cholangitis (PSC) patients compared to normal and diseased controls. There are three groups of patients. (1) Normal donor controls (ND), (2) Patients with Primary Sclerosing Cholangitis (PSC), and (3) Disease Controls (DC) which are patients with liver disease other than PSC.
INSTITUTE
Mayo Clinic
LAST_NAME
O'Hara
FIRST_NAME
Steven
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Acyl Carnitines Concentrations of Primary Sclerosing Cholangitis (part III)
STUDY_SUMMARY
To qualitatively and quantitatively analyze enterohepatically-circulated molecules using targeted acyl carnitines concentrations of peripheral blood collected from primary sclerosing cholangitis (PSC) patients compared to normal and diseased controls. There are three groups of patients. (1) Normal donor controls (ND), (2) Patients with Primary Sclerosing Cholangitis (PSC), and (3) Disease Controls (DC) which are patients with liver disease other than PSC.
INSTITUTE
Mayo Clinic
LAST_NAME
O'Hara
FIRST_NAME
Steven
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Bile Acid of Primary Sclerosing Cholangitis (part IV)
STUDY_SUMMARY
To qualitatively and quantitatively analyze enterohepatically-circulated molecules using targeted bile acid concentrations of peripheral blood collected from primary sclerosing cholangitis (PSC) patients compared to normal and diseased controls. There are three groups of patients. (1) Normal donor controls (ND), (2) Patients with Primary Sclerosing Cholangitis (PSC), and (3) Disease Controls (DC) which are patients with liver disease other than PSC.
INSTITUTE
Mayo Clinic
LAST_NAME
O'Hara
FIRST_NAME
Steven
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Untargeted high-resolution mass spectrometry profiling
STUDY_SUMMARY
Urban environments remain a poorly understood toxic environment for children with asthma, where improved exposure characterization and estimation of exposurehealth outcome relationships are clearly needed. The goal of this project is to investigate the interactions between relevant environmental exposures and asthma severity in a year-long longitudinal study of urban children with asthma. Environmental and clinical samples are being collected at 3 seasonal visits. Using these samples, we will measure the effects of multiple relevant exposures (environmental tobacco smoke (ETS), polycyclic aromatic hydrocarbons (PAHs), phthalates, and volatile organic compounds (VOCs)) on biological responses (metabolomics, oxidative stress, inflammatory markers, and endocannabinoids) and asthma outcomes. Our overall hypothesis is that relevant environmental exposures and their interactions drive disease severity in urban children with asthma. We will test this hypothesis by investigating the following aims: Aim 1: To investigate how environmental exposures (ETS, PAHs, phthalates, and VOCs) and their interactions contribute to asthma severity in urban children. Aim 2: To determine if environmental exposures in children with asthma are associated with changes in in biological responses (metabolomics, oxidative stress, inflammatory markers, and endocannabinoids). Aim 3: To determine which biological responses mediate the relationships between environmental exposures and asthma severity. Aim 4: To compare environmental exposures and biological responses in asthmatic and non-asthmatic children
INSTITUTE
Emory University
DEPARTMENT
School of Medicine
LABORATORY
Clincal Biomarkers Laboratory
LAST_NAME
Uppal
FIRST_NAME
Karan
ADDRESS
615 Michael St. Ste 225, Atlanta, GA, 30322, USA
EMAIL
kuppal2@emory.edu
PHONE
(404) 727 5027
TOTAL_SUBJECTS
66
STUDY_COMMENTS
Both CHEAR and Clinical Biomarker Laboratory pooled plasma samples were used for quality control. Study specific sample pools were not created
Amino Acid Concentrations in Muscle Tissue of Muscle Wasting in Cancer Cachexia (part I)
STUDY_SUMMARY
Amino Acid Concentrations of Muscle Wasting in Cancer Cachexia. Muscle samples from 10 control patients, 10 weight stable pancreatic cancer patients, and 10 pancreatic cancer patients with significant weight loss. Samples are divided evenly between males and females.
INSTITUTE
Mayo Clinic
LAST_NAME
Guttridge
FIRST_NAME
Denis
ADDRESS
520 Biomedical Research Tower 460 W. 12th Avenue Columbus, OH 43210
TCA Concentrations in Muscle Tissue of Muscle Wasting in Cancer Cachexia (part II)
STUDY_SUMMARY
TCA Concentrations of Muscle Wasting in Cancer Cachexia. Muscle samples from 10 control patients, 10 weight stable pancreatic cancer patients, and 10 pancreatic cancer patients with significant weight loss. Samples are divided evenly between males and females.
INSTITUTE
Mayo Clinic
LAST_NAME
Guttridge
FIRST_NAME
Denis
ADDRESS
520 Biomedical Research Tower 460 W. 12th Avenue Columbus, OH 43210
Acyl Carnitines Concentrations in Muscle Tissue of Muscle Wasting in Cancer Cachexia (part-IV)
STUDY_SUMMARY
Acyl Carnitines Concentrations of Muscle Wasting in Cancer Cachexia. Muscle samples from 10 control patients, 10 weight stable pancreatic cancer patients, and 10 pancreatic cancer patients with significant weight loss. Samples are divided evenly between males and females.
INSTITUTE
Mayo Clinic
LAST_NAME
Guttridge
FIRST_NAME
Denis
ADDRESS
520 Biomedical Research Tower 460 W. 12th Avenue Columbus, OH 43210
NEFA Panel in Muscle Tissue of Muscle Wasting in Cancer Cachexia (part-V)
STUDY_SUMMARY
NEFA Panel of Muscle Wasting in Cancer Cachexia. Muscle samples from 10 control patients, 10 weight stable pancreatic cancer patients, and 10 pancreatic cancer patients with significant weight loss. Samples are divided evenly between males and females.
INSTITUTE
Mayo Clinic
LAST_NAME
Guttridge
FIRST_NAME
Denis
ADDRESS
520 Biomedical Research Tower 460 W. 12th Avenue Columbus, OH 43210
NEFA Panel in Serum for Muscle Wasting in Cancer Cachexia (part-VI)
STUDY_SUMMARY
NEFA Panel of Muscle Wasting in Cancer Cachexia. Serum samples from 10 control patients, 10 weight stable pancreatic cancer patients, and 10 pancreatic cancer patients with significant weight loss. Samples are divided evenly between males and females.
INSTITUTE
Mayo Clinic
LAST_NAME
Guttridge
FIRST_NAME
Denis
ADDRESS
520 Biomedical Research Tower 460 W. 12th Avenue Columbus, OH 43210
Amino Acid Concentrations in Serum for Muscle Wasting in Cancer Cachexia (part-VII)
STUDY_SUMMARY
Amino Acid Concentrations of Muscle Wasting in Cancer Cachexia. Serum samples from 10 control patients, 10 weight stable pancreatic cancer patients, and 10 pancreatic cancer patients with significant weight loss. Samples are divided evenly between males and females.
INSTITUTE
Mayo Clinic
LAST_NAME
Guttridge
FIRST_NAME
Denis
ADDRESS
520 Biomedical Research Tower 460 W. 12th Avenue Columbus, OH 43210
TCA Concentrations in Serum for Muscle Wasting in Cancer Cachexia (part-VIII)
STUDY_SUMMARY
TCA Concentrations of Muscle Wasting in Cancer Cachexia. Serum samples from 10 control patients, 10 weight stable pancreatic cancer patients, and 10 pancreatic cancer patients with significant weight loss. Samples are divided evenly between males and females.
INSTITUTE
Mayo Clinic
LAST_NAME
Guttridge
FIRST_NAME
Denis
ADDRESS
520 Biomedical Research Tower 460 W. 12th Avenue Columbus, OH 43210
Sphingolipid Concentrations in Serum for Muscle Wasting in Cancer Cachexia (part-IX)
STUDY_SUMMARY
Sphingolipid Concentrations of Muscle Wasting in Cancer Cachexia. Serum samples from 10 control patients, 10 weight stable pancreatic cancer patients, and 10 pancreatic cancer patients with significant weight loss. Samples are divided evenly between males and females.
INSTITUTE
Mayo Clinic
LAST_NAME
Guttridge
FIRST_NAME
Denis
ADDRESS
520 Biomedical Research Tower 460 W. 12th Avenue Columbus, OH 43210
Acyl Carnitines Concentration in Serum for Muscle Wasting in Cancer Cachexia (part-X)
STUDY_SUMMARY
Acyl Carnitines Concentrations of Muscle Wasting in Cancer Cachexia. Serum samples from 10 control patients, 10 weight stable pancreatic cancer patients, and 10 pancreatic cancer patients with significant weight loss. Samples are divided evenly between males and females.
INSTITUTE
Mayo Clinic
LAST_NAME
Guttridge
FIRST_NAME
Denis
ADDRESS
520 Biomedical Research Tower 460 W. 12th Avenue Columbus, OH 43210
Sphingolipid Concentrations in Muscle Tissue of Muscle Wasting in Cancer Cachexia (part-III)
STUDY_SUMMARY
Sphingolipid Concentrations of Muscle Wasting in Cancer Cachexia. Muscle samples from 10 control patients, 10 weight stable pancreatic cancer patients, and 10 pancreatic cancer patients with significant weight loss. Samples are divided evenly between males and females.
INSTITUTE
Mayo Clinic
LAST_NAME
Guttridge
FIRST_NAME
Denis
ADDRESS
520 Biomedical Research Tower 460 W. 12th Avenue Columbus, OH 43210
H3K27M cells and glutamine metabolomics 1 million cell test (part-I)
STUDY_SUMMARY
Testing TCA concentrations of Diffuse Intrinsic Pontine Gliomas (DIPG) cellines with H3K27M mutations. One million cells are tested with a TCA concentrations panel. We are a high volume center for treating malignant gliomas, which gives us an advantage in obtaining tissue for these relatively rare tumors. We have developed several DIPG patient derived cell lines and xenografts that bear all the key molecular features of this disease including the H3K27M mutation and global H3K27 hypomethylation. These cells are low in passage and we think these lines more closely resemble the patients tumor pathology then established cell lines that have been in culture/mice for numerous years.
TCA cycle metabolomics of H3K27M cells grown in regular glutamine media, glutamine free media, and glutamine free media with alpha-ketoglutarate (Part-II)
STUDY_SUMMARY
Testing TCA concentrations of Diffuse Intrinsic Pontine Gliomas (DIPG) cellines with H3K27M mutations. Preliminary studies show H3K27M tumor cells are addicted to Gln for survival. Removal of Gln from media resulted in tumor cell death which was rescued by the addition of α-KG. These data show that Gln is taken up and metabolized by H3K27M tumor cells and that Gln derived α-KG is critical for the survival of these tumors. Interestingly, tumor cell death with Gln deprivation was similar to the effect of the JMJD3 inhibitor GSKJ4. Therefore, Gln derived α-KG may be required for both anaplerosis and to drive JMJD3 demethylation. We hypothesize that H3K27M tumors are reliant on α-KG that is derived from Gln to drive the TCA cycle and further decrease H3K27 methylation levels. Furthermore, inhibition of Gln metabolism may represent a novel therapeutic approach for tumors with this mutation. In this study, TCA cycle metabolomics are analyzed of H3K27M cells grown in regular glutamine media, glutamine free media, and glutamine free media with alpha-ketoglutarate.
TCA Isotopmer metabolomics of H3K27M Cells grown in regular media, glutamine enriched regular media, and glucose encriched regular media (Part-III)
STUDY_SUMMARY
TCA Isotopmer metabolomics of H3K27M Cells grown in regular media, glutamine enriched regular media, and glucose encriched regular media. TCA isotopomers traced for 0, 12, or 24 hours were measured.
TCA cycle metabolomics of H3K27M Cell Nucleus Fraction and Cell Mitonchonrdial Fraction (Part-IV)
STUDY_SUMMARY
Testing TCA concentrations of Diffuse Intrinsic Pontine Gliomas (DIPG) cellines with H3K27M mutations. Preliminary studies show H3K27M tumor cells are addicted to Gln for survival. Removal of Gln from media resulted in tumor cell death which was rescued by the addition of α-KG. These data show that Gln is taken up and metabolized by H3K27M tumor cells and that Gln derived α-KG is critical for the survival of these tumors. Interestingly, tumor cell death with Gln deprivation was similar to the effect of the JMJD3 inhibitor GSKJ4. Therefore, Gln derived α-KG may be required for both anaplerosis and to drive JMJD3 demethylation. We hypothesize that H3K27M tumors are reliant on α-KG that is derived from Gln to drive the TCA cycle and further decrease H3K27 methylation levels. Furthermore, inhibition of Gln metabolism may represent a novel therapeutic approach for tumors with this mutation. In this study, TCA cycle metabolomics are analyzed of H3K27M cells grown in regular glutamine media, glutamine free media, and glutamine free media with alpha-ketoglutarate. Additionally, cell nucleus and cell mitochrondial fractions are run separately.
Metabolic profiling of identified single cells in Xenopus laevis embryos
STUDY_TYPE
Metabolic profiling of single cells
STUDY_SUMMARY
Single D11 cells were identified in 16-cell embryos of Xenopus laevis. Metabolites were extracted, and the extracts were analyzed using a custom-built capillary electrophoresis electrospray ionization platform coupled to a quadrupole time-of-flight mass spectrometer. The resulting metadata was analyzed by Trace, a custom-design software, designed to extract molecular feautres from trace-sensitive metabolomics experiments. The results were validated against molecular features that were extracted by manual curation of the same raw mass spectrometer files.
INSTITUTE
University of Maryland
DEPARTMENT
Department of Chemistry & Biochemistry
LABORATORY
Nemes Laboratory
LAST_NAME
Nemes
FIRST_NAME
Peter
ADDRESS
0107 Chemistry Building, 8051 Regents Dr, College Park, MD 20742
EMAIL
nemes@umd.edu
PHONE
3014050373
NUM_GROUPS
5 biological replicates (different cells from different embryos) + 1-to-3 technical replicates (same extract analyzed multiple times)
TOTAL_SUBJECTS
5 different D11 cells were analyzed, each from a different embryo
PUBLICATIONS
Trace: Machine Learning of Signal Images for Trace-Sensitive Mass Spectrometry – A Case Study from Single-Cell Metabolomics
Single-cell Profiling of Cationic and Anionic Metabolites in Live Frog (Xenopus) Embryos using Microprobe Capillary Electrophoresis Mass Spectrometry
STUDY_TYPE
Metabolic profiling of single cells
STUDY_SUMMARY
The goal of this study was to enable the analysis of anionic and cationic metabolites from the same identified single cell in Xenopus laevis embryos. A 10 nL portion of identified animal-ventral (V1) cells was aspirated from 8-cell embryos, and metabolites were extracted from the aspirate, before characterization of cationic and anionic compounds using a custom-built capillary electrophoresis (CE) electrospray ionization (ESI) mass spectrometry platform. A total of ~250 cationic molecular features and ~150 anionic molecular features were detected, including 76 metabolites that were identified in this study. Pathway analysis of the identified metabolites highlighted arginine-proline metabolism of significance.
INSTITUTE
University of Maryland
DEPARTMENT
Department of Chemistry & Biochemistry
LABORATORY
Nemes Laboratory
LAST_NAME
Nemes
FIRST_NAME
Peter
ADDRESS
0107 Chemistry Building 8051 Regents Drive
EMAIL
nemes@umd.edu
PHONE
3014050373
NUM_GROUPS
4 biological replicates (each different cell from a different embryo) + 1-to-2 technical replicates (same extract analyzed multiple times)
TOTAL_SUBJECTS
4 different V1 cells were analyzed, each from a different embryo
TCA Isotopomers in Neuromyelitis Optica Patients (part - I)
STUDY_SUMMARY
Patients with an inflammatory disease of the central nervous system known as neuromyelitis optica (NMO) experience increased levels of depression. These patients have an antibody that recognizes a type of cell in the brain called astrocytes – binding of this antibody to astrocytes triggers a stress response in the cell that results in the development of brain lesions that cause disability and cognitive disturbances. We recently observed a change in the level of glutamate in a part of the brain involved in depression in patients with NMO. Glutamate is a chemical that is used in the brain for communication between neurons – reduced levels of glutamate are thought to trigger depression by reducing neuronal activity in specific circuits. Based on this observation and the known role of astrocytes in maintaining glutamate levels in the brain, we hypothesize that the NMO antibody disturbs metabolic activity in astrocytes and thereby reduces glutamate and triggers depression. We intend to trace the metabolic response induced in astrocytes by the NMO antibody using TCA isotopomers. It is our hope that we will not only learn something about the mechanisms of astrocyte dysregulation in neuromyelitis optica, but that we will learn something about the mechanisms of depression in general that may lead to new therapies for this disease.
INSTITUTE
Mayo Clinic
LAST_NAME
Howe
FIRST_NAME
Charles
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
TCA Concentrations in Neuromyelitis Optica Patients (part - II)
STUDY_SUMMARY
Patients with an inflammatory disease of the central nervous system known as neuromyelitis optica (NMO) experience increased levels of depression. These patients have an antibody that recognizes a type of cell in the brain called astrocytes – binding of this antibody to astrocytes triggers a stress response in the cell that results in the development of brain lesions that cause disability and cognitive disturbances. We recently observed a change in the level of glutamate in a part of the brain involved in depression in patients with NMO. Glutamate is a chemical that is used in the brain for communication between neurons – reduced levels of glutamate are thought to trigger depression by reducing neuronal activity in specific circuits. Based on this observation and the known role of astrocytes in maintaining glutamate levels in the brain, we hypothesize that the NMO antibody disturbs metabolic activity in astrocytes and thereby reduces glutamate and triggers depression. We intend to measure TCA concentration in NMO astrocytes. It is our hope that we will not only learn something about the mechanisms of astrocyte dysregulation in neuromyelitis optica, but that we will learn something about the mechanisms of depression in general that may lead to new therapies for this disease.
INSTITUTE
Mayo Clinic
LAST_NAME
Howe
FIRST_NAME
Charles
ADDRESS
200 First St. SW, Rochester, Minnesota, 55905, USA
Global Metabolomics of the Placenta Reveals Distinct Metabolic Profiles between Maternal and Fetal Placental Tissues Following Delivery in Non-Labored Women
STUDY_TYPE
Timecourse
STUDY_SUMMARY
We evaluated the metabolic alterations in maternal and fetal placental tissues from non-labored women undergoing cesarean section using samples collected from 5 min to 24 h following delivery. Using 1H-NMR, we identified 14 metabolites that significantly differed between maternal and fetal placental tissues (FDR-corrected p-value < 0.05), with 12 metabolites elevated in the maternal tissue, reflecting the flux of these metabolites from mother to fetus. In the maternal tissue, 4 metabolites were significantly altered at 15 min, 10 metabolites at 30 min, and 16 metabolites at 1 h postdelivery, while 11 metabolites remained stable over 24 h. In contrast, in the fetal placenta tissue, 1 metabolite was significantly altered at 15 min, 2 metabolites at 30 min, and 4 metabolites at 1 h postdelivery, while 22 metabolites remained stable over 24 h. Our study provides information on the metabolic profiles of maternal and fetal placental tissues delivered by cesarean section and reveals that there are different metabolic alterations in the maternal and fetal tissues of the placenta following delivery.
INSTITUTE
University of Florida
DEPARTMENT
Biochemistry & Molecular Biology
LAST_NAME
Jacquelyn
FIRST_NAME
Walejko
ADDRESS
R3-226 Academic Research Building, Department of Biochemistry and Molecular Biology, PO Box 100245, Gainesville, FL 32610-0245
Denver Asthma Panel Study-CHEAR Ancillary Study (part II)
STUDY_SUMMARY
Urban environments remain a poorly understood toxic environment for children with asthma, where improved exposure characterization and estimation of exposurehealth outcome relationships are clearly needed. The goal of this project is to investigate the interactions between relevant environmental exposures and asthma severity in a year-long longitudinal study of urban children with asthma. Environmental and clinical samples are being collected at 3 seasonal visits. Using these samples, we will measure the effects of multiple relevant exposures (environmental tobacco smoke (ETS), polycyclic aromatic hydrocarbons (PAHs), phthalates, and volatile organic compounds (VOCs)) on biological responses (metabolomics, oxidative stress, inflammatory markers, and endocannabinoids) and asthma outcomes. Our overall hypothesis is that relevant environmental exposures and their interactions drive disease severity in urban children with asthma. We will test this hypothesis by investigating the following aims: Aim 1: To investigate how environmental exposures (ETS, PAHs, phthalates, and VOCs) and their interactions contribute to asthma severity in urban children. Aim 2: To determine if environmental exposures in children with asthma are associated with changes in in biological responses (metabolomics, oxidative stress, inflammatory markers, and endocannabinoids). Aim 3: To determine which biological responses mediate the relationships between environmental exposures and asthma severity. Aim 4: To compare environmental exposures and biological responses in asthmatic and non-asthmatic children
INSTITUTE
Emory University
DEPARTMENT
School of Medicine
LABORATORY
Clincal Biomarkers Laboratory
LAST_NAME
Uppal
FIRST_NAME
Karan
ADDRESS
615 Michael St. Ste 225, Atlanta, GA, 30322, USA
EMAIL
kuppal2@emory.edu
PHONE
(404) 727 5027
TOTAL_SUBJECTS
169
STUDY_COMMENTS
Both CHEAR pooled urine samples and Clinical Biomarker Laboratory pooled plasma samples were used
Pediatric Inner-City Environmental Exposures at School and Home and Asthma Study
STUDY_TYPE
CHEAR Study
STUDY_SUMMARY
SICAS 1 and SICAS 2 have extraordinary opportunity to evaluate the role of diet, environmental exposures and asthma in the context of school and home specific exposures and capitalize on all the data we are already collecting. Asthma affects 25 million Americans, particularly urban minority children. Children spend nearly all day in school, yet little is known about the role of a child’s exposure to widely disseminated industrial chemicals on asthma morbidity. Early animal models and population studies have begun to identify an association between phenolic chemical exposure and asthma development through proposed increased regulation of an individual’s allergic immune response. This study, nested within a school-based environmental intervention trial, (School Inner-City Asthma Intervention Study, SICAS2) , will enable urinary biomarker analyses during a school-based academic year-long environmental intervention trial to analyze the source and impact of exposures on urinary environmental exposure biomarker levels as well as the relationship between these biomarkers levels and asthma morbidity. We are poised to leverage the clinical and exposure data being collected in the clinical trial and generate cross-sectional urinary phenol biomarker data (at baseline) within the resources of CHEAR. If successful, our study will assess the impact of exposures on these biomarker levels and the impact that these exposures have on asthma morbidity, controlling comprehensively for other personal, home, and school environmental factors associated with asthma outcomes. We hypothesize that exposure to environmental exposures (e.g. phenols, phthalates, environmental tobacco smoke) in urban school children and higher urinary biomarkers will preliminarily be associated with higher asthma morbidity. Specific aims are: Aim 1. To determine the source of exposure to environmental exposures (e.g. phenols, phthalates, environmental tobacco smoke) in inner-city school children as assessed by questionnaire, product use assessment and comprehensive school and home environmental assessment of children with physician-diagnosed asthma. Aim 2. To determine whether urinary phenol/phathalate/cotinine biomarkers are associated with asthma control (e.g. asthma symptoms, such as asthma-related symptom days (primary outcome), and other phenotypes of asthma/allergic symptoms and inflammation such as allergic sensitization, health care utilization and pulmonary lung function
INSTITUTE
Icahn School of Medicine at Mount Sinai
DEPARTMENT
Department of Environmental Medicine and Public Health
Lipidomics for wildlife disease etiology and biomarker discovery: a case study of pansteatitis outbreak in South Africa (part-I)
STUDY_TYPE
lipidomics
STUDY_SUMMARY
Lipidomics is a promising tool to determine biomarkers and elucidate mechanisms associated with anthropogenic-induced stress in wildlife. Therefore, we examine the application of lipidomics for in situ studies on Mozambique tilapia (Oreochromis mossambicus) in Loskop Dam, South Africa. Mortality events of aquatic life associated with an environmentally-derived inflammatory disease, pansteatitis, have occurred in this area. The lipidome of adipose tissue (n = 31) and plasma (n = 51) from tilapia collected from at Loskop Dam were characterized using state of the art liquid chromatography coupled to high-resolution tandem mass spectrometry. Lipid profiles reflected pansteatitis severity and were significantly different between diseased and healthy individuals. Over 13 classes of lipids associated with inflammation, cell death, and/or oxidative damage were upregulated in pansteatitis-affected adipose tissue, including ether-lipids, short-chained triglyceride oxidation products, sphingolipids, and acylcarnitines. Ceramides showed a 1000-fold increase in the most affected adipose tissues, illustrating its potential as sensitive and novel indicators of disease severity. In plasma, triglycerides were found to be downregulated in pansteatitis-affected tilapia. As comprehensive coverage of the lipidome aids in the elucidation of possible disease mechanisms, application of lipidomics could be applied to the understanding of other environmentally-derived inflammatory conditions, such as those caused by obesogens.
INSTITUTE
South East Center for Integrated Metabolomics
DEPARTMENT
Department of Pathology, Immunology and Laboratory Medicine
LABORATORY
SECIM
LAST_NAME
Koelmel
FIRST_NAME
Jeremy
ADDRESS
Department of Pathology, Immunology and Laboratory Medicine, University of Florida, 1395 Center Dr, Room M641c
EMAIL
jeremykoelmel@gmail.com
PHONE
7187300454
NUM_GROUPS
8
TOTAL_SUBJECTS
51
NUM_MALES
28
NUM_FEMALES
23
STUDY_COMMENTS
Adipose and plasma do not overlap exactly in subjects ran
1H-NMR Analysis of Skin and Blubber of Nose Dolphin Metabolome Reveal the Functional Metabolomic Dichotomy of The Organs
STUDY_TYPE
Dolphin Skin and Blubber
STUDY_SUMMARY
The common bottlenose dolphin (Tursiops truncatus) is carnivorous cetacean thriving in marine environment are one of the most common apex predators found in coastal and estuarine ecosystems. Although recent studies have focused on capturing the circulating metabolomes of these organisms, with respect to pollutants and exposures of the marine environment, the skin and blubber are important protective organs that have not been probed. Using 1HNMR based untargeted metabolomics we quantified 51 metabolites belonging to 74 different metabolic pathways in the skin and blubber of bottle nose dolphins (n=5) samples collected in 2017 from the coast of Mexico. Results indicate that the skin and blubber metabolism are quantitatively different. These metabolite abundances could help discriminate the tissue-types using supervised and unsupervised PCA and PLSDA analysis. Heat maps and random forest analysis point to unique metabolites that are important classifiers of the tissue-type. The altered metabolic patterns, mainly linking fatty acid metabolism and ketogenic amino acids, seem to constitute a characteristic of blubber, while the skin showed diverse metabolites involved in gluceoneogenic pathways. 1H NMR spectra allowed the identification of metabolites associated with these organ types, such as pyruvic acid, arginine, ornithine, 2-hydroxybutyric acid, 3-hydroxyisobutyric acid, and acetic acid, as discriminatory and classifying metabolites. These results would lead to further understanding of dolphin skin and blubber metabolism for better efforts in their conservation as well as a measure of marine pollution and ecotoxicology.
INSTITUTE
Wake Forest Baptist Medical Center
DEPARTMENT
Department of Internal Medicine
LAST_NAME
Misra
FIRST_NAME
Biswapriya
ADDRESS
Medical Center Boulevard NRC Building, G#43, Medical Center Boulevard, Winston Salem, NC, 27157, USA
Fingerprinting gastrointestinal diseases by 1H NMR
STUDY_SUMMARY
We studied 64 patients admitted to the Florence main hospital emergency room with severe abdominal pain. A blood sample was drawn from each patient at admission, and the corresponding sera underwent 1H NMR metabolomics fingerprinting. Unsupervised PCA analysis showed a significant discrimination between a group of patients with symptoms of upper abdominal pain and a second group consisting of patients with diffuse abdominal/intestinal pain. Prompted by this observation, supervised statistical analysis (OPLS-DA) showed a very good discrimination (> 90 %) between the two groups of symptoms. Actually in the present study, upper abdominal pain may result from either symptomatic gallstones, cholecystitis or pancreatitis, while diffuse abdominal/intestinal pain may result from either intestinal ischemia, strangulated obstruction or mechanical obstruction. Although limited by the small number of samples from each of these six conditions, discrimination of these diseases was attempted. In the first symptom group, > 70% discrimination accuracy was obtained among symptomatic gallstones, pancreatitis and cholecystitis, while for the second symptom group > 85% classification accuracy was obtained for intestinal ischemia, strangulated obstruction and mechanical obstruction. No single metabolite stands up as a possible biomarker for any of these diseases, while the contribution of the whole 1H NMR serum fingerprint seems to be a promising candidate, to be confirmed on larger cohorts, as a first-line discriminator for these diseases.
Evaluation of the short-term effects of the allelochemical umbelliferone on Triticum durum L. metabolism through GC-MS based untargeted metabolomics
STUDY_SUMMARY
Allelopathy is a plant defense mechanism by which they protect themselves from competitive species using specialized biochemicals in the form of secretion or volatiles released to the environment. Though, umbelliferone is a well-known allelochemical, its mechanism of action in a short-term treatment is far from established. We used ≈ 10–days old wheat seedlings treated with104 µM umbelliferone over a time course experiment covering 6 times points, i.e., 0h, 6h, 12h, 24h, 48h, and 96h and compared the metabolomic changes to control (mock-treated) plants. Using gas chromatography mass-spectrometry (GC-MS) based metabolomics efforts, we collectively obtained quantitative data on 177 metabolites that were derivatized (either derivatized singly or multiple times) or not representing 139 non-redundant (unique) metabolites. Out of these 139 metabolites, 118 were associated with a unique HMDB identifier, while 113 were associated with a KEGG identifier. Relative quantification of these metabolites across the time-course of umbelliferone treatment, revealed 22 compounds (sugars, fatty acids, secondary metabolites, organic acids, and amino acids) that changed significantly (repeated measures ANOVA, P-value < 0.05) with time. Using multivariate partial least squares discriminant analysis (PLS-DA) we showed the grouping of samples based on time-course across the control and umbelliferone treated plants, whereas the metabolite-metabolite Pearson correlation revealed tightly formed clusters of umbelliferone-derived metabolites, fatty acids, amino acids, and carbohydrates. Also, time-course of umbelliferone treatment revealed, that phospho-L-serine, maltose, and dehydroquinic acid were the top three metabolites showing highest importance in discrimination among the time-points. The above indicate a system-wide changes induced by umbelliferone, through dysregulation of primary as well as specialized metabolism.
INSTITUTE
Università Mediterranea di Reggio Calabria
DEPARTMENT
Dipartimento AGRARIA
LAST_NAME
Araniti
FIRST_NAME
Fabrizio
ADDRESS
Department AGRARIA, University Mediterranea of Reggio Calabria, Località Feo di Vito, SNC I-89124, Reggio Calabria RC, Italy
Glutathione (GSH) is a tripeptide that is implicated in various crucial physiological processes including redox buffering and protection against heavy metal toxicity. GSH is abundant in plants, with reported intracellular concentrations typically in the 1-10 millimolar range. Various aminotransferases can inadvertently transaminate the amino group of the γ-glutamyl moiety of GSH to produce deaminated glutathione (dGSH), a metabolite damage product. It was recently reported that an amidase known as Nit1 participates in dGSH breakdown in mammals and yeast. Plants have a hitherto uncharacterized homolog of the Nit1 amidase. We show that recombinant Arabidopsis Nit1 (At4g08790) has efficient amidase activity towards dGSH. Ablating the Arabidopsis Nit1 gene causes a massive accumulation of dGSH and other marked changes to the metabolome. All plant Nit1 sequences examined had predicted plastidial targeting peptides with a potential second start codon whose use would eliminate the targeting peptide. In vitro transcription/translation assays show that both potential translation start codons were used and subcellular localization of GFP fusions confirmed both cytosolic and plastidial localization. Further, we show that Arabidopsis enzymes convert GSH to dGSH at a rate of 2.8 pmol min-1 mg-1 in vitro. Our data demonstrate that plants have a dGSH repair system that is directed to at least two subcellular compartments via the use of alternative translation start sites.
Nude mice orthotopicly implanted with human glioma cell lines
STUDY_SUMMARY
Malignant gliomas are considered to be one of the deadliest human cancers, accounting for about 60% of all primary brain tumors. Cachexia is a complex metabolic derangement and muscle atrophy syndrome, which causes high mortalities in patients with advanced cancers including brain tumors. However, cachexia symptoms induced by gliomas and mechanisms underlying muscle atrophy are unclear. Herein, we developed a glioma cachexia model using nude mice orthotopicly implanted with two glioma cell lines (WHO II CHG5 and WHO IV U87). U87 mice developed more severe cachexia symptoms than CHG5 mice, including more evident anorexia, greater body weight loss and mortality. Unlike non-central nervous system cancer cachexia, glioma cachexia did not induce remarkable systemic inflammation but massive multi-organ atrophy. It also caused significantly decreased skeletal muscle mass and strength, which were associated with down-regulated myosin and AKT, and up-regulated AMPK, FOXO and Atrogin1. Interestingly, expressions of MuRF1, MyoD1, eIF3f, desmin and vimentin were not significantly changed. Consistently, NMR-based metabolomic analyses revealed pronounced metabolic derangements in cachectic gastrocnemius relative to controls. Glucose, glycerol, 3-hydroxybutyrate and glycine were remarkably down-regulated, whereas largely released amino acids due to proteolysis including glutamate, arginine, leucine and isoleucine were up-regulated in cachectic gastrocnemius. Moreover, glucose and lipid metabolism, protein biosynthesis and amino acid metabolism were disturbed dramatically in both glioma-bearing mice. U87 mice showed more changed metabolite levels and altered metabolic pathways. This work uncovers malignant grade-dependent glioma cachexia symptoms and metabolic derangements of skeletal muscle for the first time, and provides hints for new therapeutic approaches.
Evaluation of Seryl-leucine core 1 O-glycosylated peptide (SLC1G) in TB patient urine
STUDY_SUMMARY
Previous work detected an uncharacterized urine metabolite with a molecular mass of 874.3547 Da that showed promise as a biomarker for successful TB treatment. Using mass spectrometry combined with enzymatic digestions, the metabolite was structurally characterized as a seryl-leucine core 1 O-glycosylated peptide (SLC1G) of human origin. Examination of SLC1G in urine revealed a significant abundance increase in individuals with active TB versus their household contacts and healthy controls. Moreover, differential decreases in SLC1G levels were observed by week-one in TB patients during successful treatment versus those that failed treatment. The SLC1G levels also associated with clinical parameters used to measure bacterial burden (GeneXpert) and inflammation (PET-CT). These results demonstrate the importance of metabolite identification and provide strong evidence for applying SLC1G as a biomarker of TB treatment response.
Combined NMR and MS Analysis of PC patien serum (part-III)
STUDY_SUMMARY
Serum of two groups of patients were analyzed using MS and NMR to find predictive markers of recurrence. Study Design factor Sample type represents samples with Recurrence (R) or No Recurrence (NR) of Cancer.
Physiological and metabolic response of crab megalopae and juveniles to ocean acidification
STUDY_SUMMARY
The objective of the study was to examine the physiological and metabolic response of crab megalopae and juveniles to ocean acidification treatment. Four treatments were used:high pH, high DO (dissolved oxygen); high pH, low DO; low pH, high DO; low pH, low DO
NMR metabolomics study of Gemcitabine resistant cancer cells
STUDY_TYPE
NMR metabolomics
STUDY_SUMMARY
1D 1H NMR spectra were collected from the samples and analyzed using MVAPACK software (http://bionmr.unl.edu/mvapack.php). Multivariate analysis was conducted to study the metabolic phenotypes of the samples.
INSTITUTE
University of Nebraska-Lincoln
DEPARTMENT
Chemistry
LABORATORY
Dr. Robert Powers and Pankaj Singh labs
LAST_NAME
Gebregiworgis
FIRST_NAME
Teklab
ADDRESS
552 Hamilton Hall, 639 N. 12th Street, Lincoln, NE, 68588, USA
Aspirin Metabolomics in Colorectal Cancer Chemoprevention (part 1 - Colon)
STUDY_TYPE
Untargeted high-resolution mass spectrometry profiling
STUDY_SUMMARY
Substantial evidence supports the effectiveness of aspirin for cancer chemoprevention in addition to its well established role in cardiovascular protection. In recent meta-analyses of randomized controlled trials in humans, daily aspirin use reduced incidence, metastasis and mortality from several common types of cancer, especially colorectal cancer. The mechanism(s) by which aspirin exerts an anticancer benefit is uncertain; numerous effects have been described involving both cyclooxygenase-dependent and -independent pathways. The goal of this research is to elucidate the key metabolic changes that are responsible for the anticancer effects of aspirin in humans using untargeted metabolomics analysis. Metabolomics, or global metabolite profiling, is an emerging discipline that has the potential to transform the study of pharmaceutical agents. Our innovative approach will use high-resolution mass spectroscopy to detect thousands of metabolites in blood plasma and normal colon mucosa biopsies that were collected from participants in the Aspirin/Folate Polyp Prevention Study, a randomized, double-blind, placebo-controlled trial of aspirin and/or folic acid supplementation for the prevention of colorectal adenomas. Participants in the trial were assigned with equal probability to three aspirin treatment arms (placebo, 81 mg, or 325 mg daily). Over the three-year treatment period, 81 mg/day of aspirin reduced the risk of adenomas, whereas the 325 mg/day dose had less effect. The aims of the current proposal are to identify metabolomic signatures, including specific metabolites and metabolic pathways, that are associated with aspirin treatment in blood and normal colon mucosal tissue of participants after three years of randomized aspirin treatment; and then to assess the associations of these metabolic signatures with adenoma risk and whether they mediate the reductions in risk due to 81 mg/day aspirin treatment. We will prioritize metabolites for study by evaluating metabolite levels in patients from the placebo and treatment arms while controlling the false discovery rate, use correlation analysis to enhance identification of relevant metabolic modules associated with these prioritized metabolites, and apply pathway mapping with post-hoc application of ion dissociation spectroscopy to representative metabolites to confirm pathway identification. Because aspirin is a multifunctional drug that is thought to modify numerous pathways with potential roles in carcinogenesis, a global discovery-based metabolomics approach is the best way to identify its key activities. The public health significance of this work is substantial because understanding the mechanism of aspirin’s anticancer effects is key to optimizing its use and to the development of novel drugs targeting the metabolic pathways identified.
INSTITUTE
Emory University
DEPARTMENT
School of Medicine
LABORATORY
Clincal Biomarkers Laboratory
LAST_NAME
Uppal
FIRST_NAME
Karan
ADDRESS
615 Michael Street, Atlanta, GA, 30322, USA
EMAIL
kuppal2@emory.edu
PHONE
(404) 727 5027
NUM_GROUPS
3
TOTAL_SUBJECTS
325
NUM_MALES
214
NUM_FEMALES
111
STUDY_COMMENTS
Both pooled colon tissue samples and Clinical Biomarker Laboratory pooled plasma samples were used
Metabolomics relies on analytical methods to provide holistic information about metabolites, their distributions across samples, and their underlying dynamic properties. The latter is gaining increasing attention due to advances in modeling and new analytical methods that provide dense time-series data. We extended high-resolution-magic angle spinning (HR-MAS) NMR—an established technique to measure metabolites from tissues and live organisms—into a flexible, untargeted, and continuous recording of in vivo metabolism. We call this technique “continuous in vivo metabolism by NMR” (CIVM-NMR). We used isotope-edited CIVM-NMR to reproduce a recent amino acid flux result in chronic lymphoid leukemia cells. We then collected untargeted CIVM-NMR datasets for Neurospora crassa, a classic multicellular model of biochemistry, genetics, and metabolism. CIVM-NMR requires virtually no sample preparation and allows for continuous collection of data over hours to days at ~4-min temporal resolution with little noise. CIVM-NMR provided real-time measurements that unambiguously reproduced the direction of flux of branched-chain amino acid accumulation in leukemia cells. It also revealed the dynamics of central carbon metabolism, amino acid metabolism, energy storage molecules, and lipid and cell wall precursors in N. crassa. CIVM-NMR is simple and readily adapted to different types of cells and microorganisms, making it ideally suited to experimentally complement kinetic models of metabolism for diverse biological systems.
INSTITUTE
University of Georgia
LAST_NAME
Judge
FIRST_NAME
Michael
ADDRESS
315 Riverbend Rd., Edison Lab, Athens, GA, 30605, USA
An untargeted metabolomics approach was utilized to determine urinary metabolites that could serve as small molecule biomarkers for treatment response to standard tuberculosis treatment. However, the majority of metabolites that most accurately distinguished patient samples at time of diagnosis from those at one month after the start of therapy lacked structural identification. The detection of unknown metabolite structures is a well-known limitation of untargeted metabolomics, and underscores a need for continued elucidation of novel metabolite structures. In this study, we sought to define the structure of a urine metabolite with an experimentally determined mass of 202.1326 Da, classified as molecular feature (MF) 874.3547. Using mass spectrometry combined with enzymatic digestions, the metabolite was structurally characterized as a seryl-leucine core 1 O-glycosylated peptide (SLC1G) of human origin.
Lipidomics of Newborn Heart Tissue Exposed to Excess Maternal Cortisol in Late Gestation (part-1)
STUDY_SUMMARY
Cardiac tissue from newborn hearts from animals exposed to excess maternal cortisol in late gestation and untreated was compared via MS lipidomic analysis
INSTITUTE
University of Florida
DEPARTMENT
Biochemsitry & Molecular Biology
LAST_NAME
Walejko
FIRST_NAME
Jacquelyn
ADDRESS
R3-226 Academic Research Building, Department of Biochemistry and Molecular Biology, PO Box 100245, Gainesville, FL 32610-0245
Screening of Breast Cancer tissue samples for alteration in the lipidome using high resolution mass spectrometer,and mapping of these changes to clinico-pathological data to search for potential bio markers
Exposure to Oral Contraceptives Alters Human Endometrial Stem Cells Culture Media Metabolomics
STUDY_SUMMARY
Although the effects of oral contraceptives (OCs) in the endometrium has been well established, its influence in the production and metabolism of endometrial mesenchymal stem cells (EnMSC) remains unclear. Therefore, we analyzed the effect of OCs in the EnMSC secretome by culture media quantitative metabolomics. The EnMSC were collected from menstrual shedding of five donors (OC group, n=3; control, non-OC group, n=2) and cultured for three passages. Cells characterization was performed by flow cytometry, and culture media was collected at the end of each passage for further quantitative metabolomics. The metabolites with higher discriminant power for sample classification were Alanine, PC aa C30:0, c4-OH-Pro, PC aa C32:2, PC ae C32:2, PC ae C40:2, glycine and PC ae C32:1 for the OC group, whereas PC aa C36:6, PC aa C34:4, SM OH C16:1, SM C26:0, PC aa C38:0, serine and PC aa C36:5 were representative of the non-OC group. This panel of metabolites showed 98% of sensitivity in sample classification according with respective groups. Altered concentrations of metabolites may be an effect of OC hormonal properties on EnMSC metabolism. Thus, this metabolomic approach could assist in the management of future stem cell therapies according to patients’ specific responses to hormone treatments.
Variability in metabolomic profiles among unique genotypes of Acropora cervicornis
STUDY_TYPE
intraspecific variability
STUDY_SUMMARY
We hypothesized that each of the three genotypes tested would have unique metabolomic profiles. These data increase our basic knowledge of the coral metabolome and represent an important step toward linking genotype, phenotype, and metabolome in reef-building corals.
INSTITUTE
University of Florida
LAST_NAME
Patterson
FIRST_NAME
Joshua
ADDRESS
Florida Aquarium Center for Conservation, 529 Estuary Shore Lane, Apollo Beach, FL 33572
Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability
STUDY_SUMMARY
Cancer cell metabolism is heavily influenced by microenvironmental factors, including nutrient availability. Therefore, knowledge of microenvironmental nutrient levels is essential to understand tumor metabolism. To measure the extracellular nutrient levels available to tumors, we developed a quantitative metabolomics method to measure the absolute concentrations of >118 metabolites in plasma and tumor interstitial fluid, the extracellular fluid that perfuses tumors. Comparison of nutrient levels in tumor interstitial fluid and plasma revealed that the nutrients available to tumors differ from those present in circulation. Further, by comparing interstitial fluid nutrient levels between autochthonous and transplant models of murine pancreatic and lung adenocarcinoma, we found that tumor type, anatomical location and animal diet affect local nutrient availability. These data provide a comprehensive characterization of the nutrients present in the tumor microenvironment of widely used models of lung and pancreatic cancer and identify factors that influence metabolite levels in tumors.
INSTITUTE
University of Chicago
LAST_NAME
Muir
FIRST_NAME
Alexander
ADDRESS
929 E 57th St. W GCIS 306, Chicago, Illinois, 60637, USA
Early Mechanistic Events Induced by Secondhand Smoke Prevalent Low Molecular Weight Polycyclic Aromatic Hydrocarbons in Mouse Lung Epithelial Cells
STUDY_SUMMARY
We evaluated lung epithelial cells exposed to low molecular weight polycyclic aromatic hydrocarbons and what lipid metabolites were produced following early exposure, prior to metabolism. For the targeted study (AKB study 2, we used 40uM dose of the 2PAHs (1methylanthracene and fluoranthene; 1:1 ratio)and assessed 2,4,8,and 12 hrs of treatment with the PAHs. We also examined a 24 h time point in another study at a lower dose (15 uM LMW PAH mixture; 1:1 ratio of 1-methanthrancene and fluoranthene).
Changes in the Canine Plasma Lipidome after Short- and Long-Term Excess Glucocorticoid Exposure
STUDY_SUMMARY
Glucocorticoids (GCs) are widely used in veterinary and human medicine. Chromic endogenous or iatrogenic GC overexposure impairs metabolic function and can result in diverse side-effects, including Cushing’s syndrome. This study examines the effects of experimentally induced short-term and long-term GC excess (induced by prednisolone and tetracosactide, respectively) on the plasma lipidome of Beale dogs. Both, long- and short-term GC resulted in significant changes of the plasma lipidome.
INSTITUTE
Life Sciences Institute, National University of Singapore
Microbial depletion and ozone exposure - Lung tissue (part I)
STUDY_SUMMARY
Global biochemical profiles were determined in lung tissue collected from untreated control mice and mice treated for two weeks with untreated drinking water or water containing an antibiotic cocktail (ampicillin, neomycin, metronidazole, and vancomycin), followed by a three hour exposure to ambient air or ozone (2ppm). Sample collection occurred 24 hours post-ozone exposure.
UPLC-MS Analysis of Lipids From Insulin Resistant Femoral Muscles of Diet-induced Obese Mice
STUDY_TYPE
Lipidomics, Basic Research
STUDY_SUMMARY
Muscle insulin resistance is a fundamental contributor in the pathogenesis of obesity-related diseases like type 2 diabetes. Increased triglyceride concentration in muscle tissue, as seen with obesity, is associated with inhibition of insulin action and decreased glucose uptake. Here we use liquid chromatography paired with mass spectrometry (LCMS) to identify patterns of lipid species in femoral muscle of mice associated with diet-induced insulin resistance. Mice were fed a standard CHOW diet for 5 weeks or HFD for 5 or 13 weeks. 806 lipids were significantly different (p ≤ 0.05) between HFD-induced insulin resistant muscle and CHOW insulin sensitive. Of these 217 lipid species were quantified and annotated based on principle components analysis, significance (p ≤ 0.01) and fold change of relative abundance values. CHOW insulin sensitive muscle was associated with triglycerides and phospholipids that contained higher abundance of long-chain highly unsaturated fatty acids. Serine and inositol phospholipids favored insulin sensitive femoral muscle, yet higher abundance also occurred in 13 week HFD mice compared with 5 week. Consequently, phospholipid imbalance may be indicative of cell membrane dysfunction. HFD insulin resistant femoral muscle contained triglycerides with less carbons, compared with CHOW, which were predominantly saturated. In addition, there was greater abundance of diacylglycerides and sphingomyelin, but not ceramides. Extending HFD intake to 13 weeks did not cause increased abundance of deleterious lipids with the exception of sphingomyelin. Overall, distinct lipid combinations, perhaps even ratios, should be characterized when identifying what contributes to the maintenance or dysregulation of muscle insulin sensitivity.
INSTITUTE
Colorado State University
DEPARTMENT
Food Science and Human Nutrition
LABORATORY
Adipose Tissue
LAST_NAME
Foster
FIRST_NAME
Michelle
ADDRESS
1571 Campus Delivery, Fort Collins, Colorado 80523
A comprehensive plasma metabolomics dataset for a cohort of mouse knockouts within the International Mouse Phenotyping Consortium
STUDY_SUMMARY
Untargeted and targeted metabolomics datasets were acquired for blood plasma samples of 30 mouse knockouts within the International Mouse Phenotyping Consortium (IMPC). http://www.mousephenotype.org/. West Coast Metabolomics Center at UC Davis (https://metabolomics.ucdavis.edu/) conducted the metabolomics analyses.
Physiological and metabolic response of pteropods to ocean acidification (part IV)
STUDY_SUMMARY
The objective of the study was to examine the physiological and metabolic response of pteropods to ocean acidification treatment. Four treatments were used:high pH, high DO (dissolved oxygen); high pH, low DO; low pH, high DO; low pH, low DO
Timecourse on MCF-7 cells treated with different concentration of doxorubicin
STUDY_SUMMARY
MCF-7 cells treated with 10μM doxorubicin for 4h followed by subsequent withdrawl of the drug and cultured up to 48h.Doxurubicin-treated cells and control cells were collected at 0,12,24,36,and 48h. Meanwhile,MCF-7 cells continuously exposed to a low dosage of doxorubicin at 0.1μM for 96h. Doxorubicin-treated cells and control cells were collected at 0,24,48,72 and 96h.
Metabolomics of World Trade Center Exposed New York City Firefighters
STUDY_TYPE
C18 Reversed-Phase Broad Spectrum Metabolomics
STUDY_SUMMARY
Particulate matter (PM) exposure and metabolic syndrome (MetSyn) coexist in both industrialized and developing nations. PM and MetSyn are strong risk factors for chronic obstructive pulmonary disease (COPD) and asthma. After the World Trade Center collapse in 9/11/2001, PM-exposed individuals from the Fire Department of New York City (FDNY) developed a progressively lung disease. This nested case-cohort study is composed of never smoking, WTC exposed firefighters with normal pre-9/11 lung function presenting for subspecialty pulmonary evaluation (SPE) before March 2008. Representative cohort controls with serum drawn within six months of 9/11 (n=100). FEV1 at subspecialty exam defined cases: susceptible World Trade Center Lung Injury (WTC-LI) cases (n=50) had FEV1< lower limit of normal (LLN) and resistant WTC-LI cases with FEV1 ≥107% predicted (n=50). This study will determine the metabolomics profile that differentiates firefighters with WTC-LI, firefighters resistant to WTC-LI, and similarly exposed cohort controls.
INSTITUTE
New York University
DEPARTMENT
School of Medicine
LABORATORY
Laboratory at NYU/Bellevue
LAST_NAME
Nolan
FIRST_NAME
Anna
ADDRESS
Academic office 462 1st Avenue, New Bellevue 16, S 16(Office)/ N 20 (Lab) New York, NY 10016
Multi-omics analysis demonstrates unique mode of action of a potent new antimalarial compound, JPC-3210, against Plasmodium falciparum
STUDY_SUMMARY
The increasing incidence of antimalarial drug resistance to the first-line artemisinins, and their combination partner drugs, underpins an urgent need for new antimalarial drugs, ideally with a novel mechanism of action. The recently developed 2-aminomethylphenol, JPC-3210, (MMV 892646) is an erythrocytic schizonticide with potent in vitro antimalarial activity against multidrug-resistant Plasmodium falciparum, low cytotoxicity, potent in vivo efficacy against murine malaria, and favourable preclinical pharmacokinetics, including a lengthy plasma elimination half-life. This study demonstrates the application of a “multi-omics” workflow based on high resolution orbitrap mass spectrometry to investigate the impact of JPC-3210 on biochemical pathways within P. falciparum infected red blood cells. Metabolomics and peptidomics analysis revealed a perturbation in hemoglobin metabolism following JPC-3210 exposure. The metabolomics data demonstrated a depletion in short hemoglobin-derived peptides, while peptidomics analysis showed a depletion in longer hemoglobin-derived peptides. In order to further elucidate the mechanism responsible for inhibition of hemoglobin metabolism, we used in vitro β-hematin polymerisation assays and showed JPC-3210 to be an intermediate inhibitor of β-hematin polymerisation, about 10-fold less potent then the quinoline antimalarials. Furthermore, quantitative proteomics analysis showed that JPC-3210 treatment results in a distinct proteomic signature in comparison to other known antimalarials. Whilst JPC-3210 clustered closely with mefloquine in the metabolomics and proteomics analyses, a key differentiating signature for JPC-3210 was the significant enrichment of parasite proteins involved in regulation of translation. In conclusion, multi-omics studies using high resolution mass spectrometry revealed JPC-3210 to possess a unique mechanism of action involving inhibition of hemoglobin digestion, depletion of DNA replication and synthesis proteins, and elevation of regulators of protein translation. Importantly, this mechanism is distinct from currently-used antimalarials, suggesting that JPC-3210 warrants further investigation as a potentially useful new antimalarial agent.
Child Health and Development Studies womb to breast cancer F0 metabolomics
STUDY_SUMMARY
We used high resolution metabolomics to understand DDT-induced alterations of in utero environment and potential health effects. This study measured endogenous metabolites in 397 maternal perinatal serum samples collected during 1959-1967 in the Child Health and Development Studies (CHDS) and assessed associations between metabolites and envrionmental chemical concentrations in maternal serum.
INSTITUTE
Emory University
LAST_NAME
Hu
FIRST_NAME
Xin
ADDRESS
Emory University Whitehead building (Rm 225), 615 Michael Street
Correlations between LC-MS/MS-detected Glycomics and NMR-detected Metabolomics in Caenorhabditis (part -I) elegans Development.
STUDY_SUMMARY
This study examines the relationship between glycans, metabolites, and development in C. elegans. Samples of N2 animals were synchronized and grown to five different time points that ranged from L1 to a mixed population of adults, gravid adults, and offspring.
Correlations between LC-MS/MS-detected Glycomics and NMR-detected Metabolomics in Caenorhabditis elegans Development.
STUDY_SUMMARY
This study examines the relationship between glycans, metabolites, and development in C. elegans. Samples of N2 animals were synchronized and grown to five different time points that ranged from L1 to a mixed population of adults, gravid adults, and offspring.
Genetic and metabolic characterization of bioengineered human fatty liver tissue with modified SIRT1 expression
STUDY_SUMMARY
Lipidomics and metabolomics was performed three types of tissue samples to compare human normal liver tissue against human NASH liver and the bioengineered human iPS-derived fatty liver tissue-iKD-SIRT1. The purpose of this study was to show that the global lipidomics profile of iPS-derived fatty liver tissue-iKD-SIRT1 was similar to that of patients with NASH
INSTITUTE
University of Pittsburgh
DEPARTMENT
Department of Pathology
LAST_NAME
Soto-Gutierrez
FIRST_NAME
Alejandro
ADDRESS
200 Lothrop Street, 423 Biomedical Science Tower, Pittsburgh, PA 15261, USA
Sepsis-related metabolic changes in ileum, jejunum, skeletal muscle, liver and lung
STUDY_SUMMARY
Rationale: Sepsis is a multi-organ disease affecting the ileum and jejunum (small intestine),liver, skeletal muscle, and lung clinically. Recently, specific alterations in circulating metabolites have been found in patients with sepsis which are thought to contribute to the pathogenesis of disease. The specific metabolic changes in the ileum, jejunum, liver, skeletal muscle, and lung have not previously been investigated. Methods: Live Pseudomonas aeruginosa isolated from a patient was given via IV catheter to pigs to induce severe sepsis. Eighteen hours later, ileum, jejunum, medial gastrocnemius skeletal muscle, liver, and lung were harvested and flash frozen. Tissues were subsequently processed for non-targeted metabolomics analysis using gas chromatography/mass spectrometry. Results: After 18 hours of sepsis, the ileum and the liver demonstrated significant changes in metabolites involved in linoleic acid metabolism, the ileum and lung had significant changes in valine/leucine/isoleucine metabolism, the jejunum, skeletal muscle, and liver had significant changes in arginine/ proline metabolism, and the skeletal muscle and lung had significant changes in aminoacyl-tRNA biosynthesis by pathway analysis. Pathway analysis also identified changes in metabolic pathways unique for different tissues, including changes in the citric acid cycle (jejunum), beta-alanine metabolism (skeletal muscle), and purine metabolism (liver). Conclusion: These findings demonstrate both overlapping metabolic pathways affected in different tissues and those that are unique to others and provide insight into the metabolic changes in sepsis leading to organ dysfunction. This may allow therapeutic interventions that focus on multiple tissues or single tissues once the relationship of the altered metabolites/metabolism to the underlying pathogenesis of sepsis is determined.
INSTITUTE
Indiana University School of Medicine
DEPARTMENT
Indiana Center for Musculoskeletal Health / Dept. of Pathology & Laboratory Medicine
MARBLES (Markers of Autism Risk in Babies: Learning Early Sign) Enriched Cohort Study: Internal Metabolomic Biomarker Exposome and Development Disorders (IMBEDD)
STUDY_SUMMARY
This project aims to identify internal biomarkers of drug, food and microbial exposures associated to Autism Spectrum Disorder (ASD) and neurodevelopmental outcomes in an enriched-risk cohort. Using targeted and untargeted internal exposome approaches to identify exposures in maternal blood and child cord blood, internal metabolomics biomarkers will be associated with related exposures and also associated with ASD.
INSTITUTE
Emory University
DEPARTMENT
School of Medicine
LABORATORY
Clincal Biomarkers Laboratory
LAST_NAME
Uppal
FIRST_NAME
Karan
ADDRESS
NA
EMAIL
kuppal2@emory.edu
PHONE
(404) 727 5027
TOTAL_SUBJECTS
147
STUDY_COMMENTS
Both CHEAR pooled plasma samples and Clinical Biomarker Laboratory pooled plasma samples were used
GC-MS Analysis of Insoluble/Polymeric Amino Acids (part-III)
STUDY_SUMMARY
Cyanobacteria are a model photoautotroph and a chassis for the sustainable production of fuels and chemicals. Yet, knowledge of photoautotrophic metabolism in the natural environment of day/night cycles is lacking yet has implications for improved yield from plants, algae, and cyanobacteria. Here, a thorough approach to characterizing diverse metabolites—including carbohydrates, lipids, amino acids, pigments, co-factors, nucleic acids and polysaccharides—in the model cyanobacterium Synechocystis sp. PCC 6803 (S. 6803) under sinusoidal diurnal light-dark cycles was developed and applied. A custom photobioreactor and novel multi-platform mass spectrometry workflow enabled metabolite profiling every 30-120 minutes across a 24-hour diurnal sinusoidal LD (“sinLD”) cycle peaking at 1,600 mol photons m 2 s-1. We report widespread oscillations across the sinLD cycle with 90%, 94%, and 40% of the identified polar/semi-polar, non-polar, and polymeric metabolites displaying statistically significant oscillations, respectively. Microbial growth displayed distinct lag, biomass accumulation, and cell division phases of growth. During the lag phase, amino acids (AA) and nucleic acids (NA) accumulated to high levels per cell followed by decreased levels during the biomass accumulation phase, presumably due to protein and DNA synthesis. Insoluble carbohydrates displayed sharp oscillations per cell at the day-to-night transition. Potential bottlenecks in central carbon metabolism are highlighted. Together, this report provides a comprehensive view of photosynthetic metabolite behavior with high temporal resolution, offering insight into the impact of growth synchronization to light cycles via circadian rhythms. Incorporation into computational modeling and metabolic engineering efforts promises to improve industrially-relevant strain design.
Targeted LC-MS/MS Analysis of Soluble Metabolites in the MeOH:H2O Phase (part-IV)
STUDY_SUMMARY
Cyanobacteria are a model photoautotroph and a chassis for the sustainable production of fuels and chemicals. Yet, knowledge of photoautotrophic metabolism in the natural environment of day/night cycles is lacking yet has implications for improved yield from plants, algae, and cyanobacteria. Here, a thorough approach to characterizing diverse metabolites—including carbohydrates, lipids, amino acids, pigments, co-factors, nucleic acids and polysaccharides—in the model cyanobacterium Synechocystis sp. PCC 6803 (S. 6803) under sinusoidal diurnal light-dark cycles was developed and applied. A custom photobioreactor and novel multi-platform mass spectrometry workflow enabled metabolite profiling every 30-120 minutes across a 24-hour diurnal sinusoidal LD (“sinLD”) cycle peaking at 1,600 mol photons m 2 s-1. We report widespread oscillations across the sinLD cycle with 90%, 94%, and 40% of the identified polar/semi-polar, non-polar, and polymeric metabolites displaying statistically significant oscillations, respectively. Microbial growth displayed distinct lag, biomass accumulation, and cell division phases of growth. During the lag phase, amino acids (AA) and nucleic acids (NA) accumulated to high levels per cell followed by decreased levels during the biomass accumulation phase, presumably due to protein and DNA synthesis. Insoluble carbohydrates displayed sharp oscillations per cell at the day-to-night transition. Potential bottlenecks in central carbon metabolism are highlighted. Together, this report provides a comprehensive view of photosynthetic metabolite behavior with high temporal resolution, offering insight into the impact of growth synchronization to light cycles via circadian rhythms. Incorporation into computational modeling and metabolic engineering efforts promises to improve industrially-relevant strain design.
Biological Responses to Tobacco Smoke Exposure in III Children: Inflammatory Processes and the Oral Microbiome
STUDY_SUMMARY
This project evaluates the biological response to overall tobacco smoke (OTS) exposure among pediatric emergency patients enrolled in a randomized-controlled intervention trial aimed at reducing secondhand smoke exposure. The effects of OTS as measured by salivary continine on salivary metabolic profiles are measured by untargeted high resolution metabolomics, comparing higher and lower levels of OTS.
INSTITUTE
Emory University
DEPARTMENT
School of Medicine
LABORATORY
Clincal Biomarkers Laboratory
LAST_NAME
Uppal
FIRST_NAME
Karan
ADDRESS
NA
EMAIL
kuppal2@emory.edu
PHONE
(404) 727 5027
TOTAL_SUBJECTS
284
STUDY_COMMENTS
Both CHEAR pooled saliva samples and Clinical Biomarker Laboratory pooled plasma samples were used
Peroxide antimalarial treatment timecourse on trophozoite-stage P. falciparum parasites
STUDY_SUMMARY
Red blood cells (RBCs) infected with trophozoite stage P. falciparum parasites (3D7 strain) at 10% parasitaemia and 2% haematocrit were treated with OZ277 (300 nM), OZ439 (300 nM), DHA (100 nM) or vehicle (0.03% DMSO). This was a 4-timepoint study, with samples taken 0, 0.5, 1.5 and 3 h after drug or vehicle addition. Samples treated with vehicle acted as the untreated control. Samples from drug treated uninfected RBCs were also taken to ensure the observed drug effects were parasite specific.
INSTITUTE
Monash University
LAST_NAME
Giannangelo
FIRST_NAME
Carlo
ADDRESS
381 Royal Parade, Parkville, Victoria, 3052, Australia
Peroxide antimalarial treatment timecourse on ring-stage P. falciparum parasites
STUDY_SUMMARY
Red blood cells (RBCs) infected with ring stage P. falciparum parasites (3D7 strain) at 10% parasitaemia and 2% haematocrit were treated with OZ277 (1 uM), OZ439 (1 uM), DHA (300 nM) or vehicle (0.03% DMSO). This was a 5-timepoint study, with samples taken 0, 1.5, 3, 6 and 9 h after drug or vehicle addition. Samples treated with vehicle acted as the untreated control. Samples from drug treated uninfected RBCs were also taken to ensure the observed drug effects were parasite specific.
INSTITUTE
Monash University
LAST_NAME
Giannangelo
FIRST_NAME
Carlo
ADDRESS
381 Royal Parade, Parkville, Victoria, 3052, Australia
Lipidomics in the serum of cold exposed mice treated with 12-LOX inhibitor LOXBlock-1
STUDY_SUMMARY
We aimed to investigate whether the cold-induced release of 12-LOX products into the circulation were dependent on 12-LOX activation. We pre-treated C57BL6/J mice with the pharmacological inhibitor LOXBlock-1 or its vehicle (DMSO), and after 15 minutes we placed them under cold temperature (5C) for 4 hours. A control group was injected with DMSO and kept at room temperature for the same 4 hours. After this period of time we, collected the blood, and obtained the serum fraction that was immediately frozen and submitted for untargeted lipidomics.
MARBLES (Markers of Autism Risk in Babies: Learning Early Sign) Enriched Cohort Study:Internal Metabolomic Biomarker Exposome and Development Disorders (IMBEDD)
STUDY_SUMMARY
This project aims to identify internal biomarkers of drug, food and microbial exposures associated to Autism Spectrum Disorder (ASD) and neurodevelopmental outcomes in an enriched-risk cohort. Using targeted and untargeted internal exposome approaches to identify exposures in maternal blood and child cord blood, internal metabolomics biomarkers will be associated with related exposures and also associated with ASD.
INSTITUTE
Emory University
DEPARTMENT
School of Medicine
LABORATORY
Clincal Biomarkers Laboratory
LAST_NAME
Uppal
FIRST_NAME
Karan
ADDRESS
NA
EMAIL
kuppal2@emory.edu
PHONE
(404) 727 5027
TOTAL_SUBJECTS
269
STUDY_COMMENTS
Both CHEAR pooled plasma samples and Clinical Biomarker Laboratory pooled plasma samples were used
Vitamin D regulates the microbiota to induce RORgt/FoxP3+ regulatory T cells
STUDY_SUMMARY
The active form of vitamin D (1,25(OH)2D) suppresses experimental models of inflammatory bowel disease in part by regulating the microbiota. In this study, the role of vitamin D in the regulation of microbe induced RORgt/FoxP3+ T regulatory (reg) cells in the colon was determined. Vitamin D sufficient (D+) mice had significantly higher frequencies of FoxP3+ and RORgt/FoxP3+ T reg cells in the colon compared to vitamin D deficient (D-) mice. The higher frequency of RORgt/FoxP3+ T reg cells in D+ colon correlated with higher numbers of bacteria from the Clostridium XIVa and Bacteroides in D+ compared to D- cecum. D- mice with fewer RORgt/FoxP3+ T reg cells were significantly more susceptible to colitis than D+ mice. Transfer of the cecal bacteria from D+ or D- mice to germfree recipients phenocopied the higher numbers of RORgt/FoxP3+ cells and reduced susceptibility to colitis in D+ versus D- recipient mice. 1,25(OH)2D treatment of the D- mice beginning at 3 weeks of age did not completely recover RORgt/FoxP3+ T reg cells or the Bacteriodes, Bacteriodes thetaiotaomicron, and Clostridium XIVa numbers to D+ values. Early vitamin D status shapes the microbiota to optimize the population of colonic RORgt/FoxP3+ T reg cells important for resistance to colitis.
INSTITUTE
The Pennsylvania State University (Penn State)
LAST_NAME
Nichols
FIRST_NAME
Robert
ADDRESS
917 Old Boalsburg Road, State College, Pennsylvania, 16801, USA
We propose to evaluate microbial and metabolic profiles in baseline and endpoint colonic mucosal, fecal, and serum samples from human patients at risk for CRC and enrolled in a 90-day phase I clinical trial. Patients will receive daily supplementation with calcium alone, a calcium-rich multimineral (Aquamin?), or placebo (maltodextrin) (n=10 per group). We hypothesize that dietary supplementation will correlate with CRC-protective metabolic profiles and that multimineral supplementation will generate more favorable profiles than calcium supplementation alone.
INSTITUTE
University of Michigan
DEPARTMENT
Biomedical Research Core Facilities
LABORATORY
Metabolomics core
LAST_NAME
Kachman
FIRST_NAME
Maureen
ADDRESS
Ann Arbor, MI
EMAIL
mkachman@med.umich.edu
PHONE
734-232-0842
NUM_GROUPS
24
TOTAL_SUBJECTS
18
STUDY_COMMENTS
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer related death when both genders are combined. Epidemiologically, calcium intake has been protective against colonic adenomas and even colon cancer. Calcium supplementation has reduced the risk of colon adenoma formation in subjects with a history of previous colon polyps. The utility of calcium supplementation for colon cancer prevention is somewhat modulated by the modest or inconsistent level of protection afforded. Our preliminary data in mice and human enterocyte models shows that dietary supplementation with a multimineral supplement (Aquamin?) containing calcium in combination with 72 measureable trace minerals is more protective against tumors and epithelial growth dysregulation than calcium alone. One potential mechanism, supported by our rodent data, is that multimineral supplementation alters gut microbial populations to generate bile acid and short chain fatty acid (SCFA) profiles that are CRC-protective.
P falciparum asexual metabolomics following drug treatment (part-I)
STUDY_SUMMARY
P falciparum infected human red blood cells were treated with 10X IC50 drug for 2.5 hours, followed by extraction and analysis of polar metabolites using HPLC-MS or HPLC-MS/MS
INSTITUTE
Penn State
LAST_NAME
Llinas
FIRST_NAME
Manuel
ADDRESS
W126 Millennium Science Complex, University Park, PENNSYLVANIA, 16802, USA
Metabolic landscape remodeling in dystrophic muscle through glucocorticoid steroid regimens
STUDY_SUMMARY
Duchenne muscular dystrophy is caused by genetic defects in the gene encoding dystrophin and leads to progressive muscle degeneration. Glucocorticoid steroids are current mainstay pharmacological regimen to decrease muscle inflammation and prolong the ambulatory period in these patients, but daily intake of glucocorticoids like prednisone and deflazacort causes adverse side effects like osteoporosis, adrenal suppression, insulin resistance and obesity. Intermittent steroid dosing has been proposed as alternative to maintain benefits and limit side effects, but a detailed understanding of the mechanisms underpinning the regimen-specific effects in muscle is still missing. Here we explore how once-daily versus once-weekly prednisone (4 week-long treatment) affect the metabolomic landscape in mdx mouse muscle (genetic model of Duchenne muscular dystrophy; DBA/2J background) through metabolomics profiling.
INSTITUTE
Northwestern University
LAST_NAME
Quattrocelli
FIRST_NAME
Mattia
ADDRESS
303 East Superior St, SQBRC 5-500, Chicago, IL, 60611, USA
Modeling the metabolic interplay between a parasitic worm and its bacterial endosymbiont allows the identification of novel drug targets
STUDY_SUMMARY
The filarial nematode Brugia malayi represents a leading cause of disability in the developing world, causing lymphatic filariasis in nearly 40 million people. Currently available drugs are not well-suited to mass drug administration efforts, so new treatments are urgently required. One potential vulnerability is the endosymbiotic bacteria Wolbachia—present in many filariae—which is vital to the worm. Genome scale metabolic networks have been used to study prokaryotes and protists and have proven valuable in identifying therapeutic targets, but only recently have been applied to eukaryotic organisms. Here, we present iDC625, the first compartmentalized metabolic model of a parasitic worm. We used this model to show how metabolic pathway usage allows the worm to adapt to different environments, and predict a set of 99 reactions essential to the survival of B. malayi. We validated three of those reactions with drug tests and demonstrated novel antifilarial properties for all three compounds.
INSTITUTE
Hospital for Sick Children, University of Toronto, NYU Langone Health
The impact of tobacco smoke exposure and environmental exposures on the pulmonary microbiome of critically ill children
STUDY_SUMMARY
This project evaluates the effects of tobacco smoke exposure (TSE) on the pediatric lung microbiome in critically ill children. The impact of TSE on the airway microbiome of critically ill, mechanically ventilated pediatric patients will be determined by through clinical outcomes and analysis of urinary and plasma metabolomes to identify other environmental exposures contributing to the alteration of the pediatric microbiome.
INSTITUTE
Emory University
DEPARTMENT
School of Medicine
LABORATORY
Clincal Biomarkers Laboratory
LAST_NAME
Uppal
FIRST_NAME
Karan
ADDRESS
NA
EMAIL
kuppal2@emory.edu
PHONE
(404) 727 5027
TOTAL_SUBJECTS
367
STUDY_COMMENTS
Both CHEAR pooled urine samples and Clinical Biomarker Laboratory pooled plasma samples were used
Plasma samples from Wistar rats fed a control or High-sodium and low-potassium HNaLK diet with or without antibiotic treatment (n = 7 each, a total of 28) were subjected to lipidomics analysis.The HNaLK diet interacts with gut bacteria to alter plasma lipid profiles, which may be related to its health effects.
Mass spectrometry-based lipidomics of oral squamous cell carcinoma tissue reveals aberrant cholesterol and glycerophospholipid metabolism
STUDY_TYPE
Case study
STUDY_SUMMARY
Comparison between the lipid profile in oral squamous cell carcinoma of the tongue and healthy epithelial tissue from the contralateral side of the tongue of the same patient.
INSTITUTE
University of Helsinki
DEPARTMENT
Department of Otorhinolaryngology-Head and Neck Cancer
LAST_NAME
Silén
FIRST_NAME
Suvi
ADDRESS
Department of Otorhinolaryngology - Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, PO Box 263, FI-00029 HUS, Helsinki, Finland
Growth cone memebrane and growth cone particulate lipidomics
STUDY_TYPE
untargeted LC-MS/MS lipidomics
STUDY_SUMMARY
We performed high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of the proteome and lipidome of GC from C57BL/6 mice across five age groups (E18, P0, P3, P6, and P9) from two growth cone fractions: growth cone membrane (GCM) and growth cone particulate (GCP)
Lipidomics Dataset of Sonication-Induced Traumatic Optic Neuropathy in Mice
STUDY_SUMMARY
Traumatic optic neuropathy (TON) is the loss of vision secondary to trauma. Approximately two weeks after traumatic damage, diffuse retinal ganglion cell loss and axon degeneration of the optic nerve are exhibited. Here we present the changes that occur in the optic nerve lipidome of two-month-old C57BL/6J mice following sonication-induced TON (SI-TON), which closely models the indirect clinical mechanism in TON. Optic nerves were harvested at three time points following injury: 1-day, 7-days, and 14-days for comparison with the control group (uninjured optic nerves from 2-month-old mice). Lipidomic changes were observed at each of the various time points, with a pattern of progression present in multiple lipid classes. This data demonstrates the distinct lipidomic changes at each time point following indirect trauma to the optic nerve.
INSTITUTE
Bascom Palmer Eye Institute, Miller School of Medicine at University of Miami, Miami, FL 33136, USA
DEPARTMENT
Ophthalmology, Bascom Palmer Eye Institute
LAST_NAME
Bhattacharya
FIRST_NAME
Sanjoy K
ADDRESS
1638 NW 10th Avenue, Suite 707A University of Miami Miami, FL, 33136
K13 mutations driving artemisinin resistance rewrite Plasmodium falciparum’s programmed intra-erythrocytic development and transform mitochondrial physiology
STUDY_SUMMARY
The emergence of artemisinin resistance in Southeast Asia, dictated by mutations in the Plasmodium falciparum k13 gene, has compromised antimalarial efficacy and created a core vulnerability in the global malaria elimination campaign. Applying quantitative transcriptomics, proteomics, and metabolomics to a panel of isogenic K13 mutant or wild-type P. falciparum lines, we observe that K13 mutations reprogram multiple aspects of intra-erythrocytic parasite biology. These changes impact its cell cycle periodicity, the unfolded protein response and protein degradation, vesicular trafficking and endocytosis, and mitochondrial functions including the TCA cycle, the electron transport chain, and redox regulation. Ring-stage artemisinin resistance mediated by the K13 R539T mutation was neutralized using atovaquone, an electron transport chain inhibitor. Our data suggest that modification of mitochondrial physiology, accompanied by other processes to reduce artemisinin’s proteotoxic effects, help protect parasites against this pro-oxidant drug, allowing resumption of growth once the rapidly-cleared artemisinins have reached sub-therapeutic levels.
INSTITUTE
Pennsylvania State University
LAST_NAME
Llinas
FIRST_NAME
Manuel
ADDRESS
W126 Millennium Science Complex, University Park, PENNSYLVANIA, 16802, USA
Macrophage-Mediated Clofazimine Sequestration is Accompanied by a Shift in Host Energy Metabolism
STUDY_TYPE
4 timepoints for urine collection, whole blood collected at sacrifice (8 weeks)
STUDY_SUMMARY
Examined the effects of long-term dosing with CFZ of mice, metabolic data on CFZ and sham mice was collected at 0, 2, 4, and 8 weeks, at 8 weeks mice were sacrificed and WB was collected from 6 CFZ treated mice and 7 sham mice
INSTITUTE
University of Michigan
DEPARTMENT
Clinical Pharmacy
LABORATORY
NMR Metabolomics Laboratory, University of Michigan
LAST_NAME
Stringer
FIRST_NAME
Kathleen
ADDRESS
College of Pharmacy, 428 Church St, Ann Arbor, MI, 48109
Subcellular organelle lipidomics in TLR-4-activated macrophages
STUDY_SUMMARY
Lipids orchestrate biological processes by acting remotely as signaling molecules or locally as membrane components that modulate protein function. Detailed insight into lipid function requires knowledge of the subcellular localization of individual lipids. We report an analysis of the subcellular lipidome of the mammalian macrophage, a cell type that plays key roles in inflammation, immune responses, and phagocytosis. Nuclei, mitochondria, endoplasmic reticulum (ER), plasmalemma, and cytoplasm were isolated from RAW 264.7 macrophages in basal and activated states. Subsequent lipidomic analyses of major membrane lipid categories identified 229 individual/isobaric species, including 163 glycerophospholipids, 48 sphingolipids, 13 sterols, and 5 prenols. Major subcellular compartments exhibited substantially divergent glycerophospholipid profiles. Activation of macrophages by the Toll-like receptor 4-specific lipopolysaccharide Kdo2-lipid A caused significant remodeling of the subcellular lipidome. Some changes in lipid composition occurred in all compartments (e.g. increases in the levels of ceramides and the cholesterol precursors desmosterol and lanosterol). Other changes were manifest in specific organelles. For example, oxidized sterols increased and unsaturated cardiolipins decreased in mitochondria, whereas unsaturated ether-linked phosphatidylethanolamines decreased in the ER. We speculate that these changes may reflect mitochondrial oxidative stress and the release of arachidonic acid from the ER in response to cell activation.
INSTITUTE
LIPID MAPS
DEPARTMENT
Multiple
LABORATORY
Multiple
LAST_NAME
Fahy
FIRST_NAME
Eoin
ADDRESS
9500 Gilman, La Jolla, CA, 92093, USA
EMAIL
efahy@ucsd.edu
PHONE
858-534-4076
PUBLICATIONS
Andreyev AY, Fahy E, Guan Z, Kelly S, Li X, McDonald JG, Milne S, Myers D, Park H, Ryan A, Thompson BM, Wang E, Zhao Y, Brown HA, Merrill AH, Raetz CR, Russell DW, Subramaniam S, Dennis EA. Subcellular organelle lipidomics in TLR-4-activated macrophages. J Lipid Res. 2010 Sep;51(9):2785-97. doi: 10.1194/jlr.M008748. Epub 2010 Jun 23. PMID: 20574076; PMCID: PMC2918461.
Regulated accumulation of desmosterol integrates macrophage lipid metabolism and inflammatory responses
STUDY_SUMMARY
To investigate the relationship between hypercholesterolemia, foam cell formation and inflammation, we performed lipidomic and transcriptomic analyses of elicited peritoneal macrophages in wild type (WT) or LDL receptor knockout (LDLR KO) mice fed either a normal cholesterol, normal fat (NCNF) diet or a high cholesterol, high fat (HCHF) 'Western' style diet. The combination of the LDLR KO genotype and the HCHF diet results in the formation of macrophage foam cells in the elicited peritoneal macrophage population. Analysis of macrophages from the above four experimental groups revealed massive reprogramming of the lipidome in response to both diet and genotype. These studies confirmed and extended prior knowledge regarding the roles of SREBP and LXR signaling in cholesterol and fatty acid homeostasis. Unexpectedly, peritoneal macrophage foam cells exhibited a strongly 'deactivated' phenotype, with marked suppression of pro-inflammatory mediators that are normally characteristic of the inflammatory responses associated with atherosclerotic lesions. Many of these changes in gene expression and lipid metabolism appear to be related to the paradoxical accumulation of high levels of desmosterol, the last intermediate in the Bloch pathway of cholesterol biosynthesis. WT or LDLR KO mice were fed either a NCNF diet or a HCHF diet for twelve weeks to establish four experimental groups (WT-NCNF diet, WT-HCHF diet, KO-NCNF diet, and KO-HCHF diet). As expected, the combination of the HCHF diet and LDLR KO genotype resulted in a synergistic effect on serum lipid levels. Elicited peritoneal macrophages (92-96% F4/80-positive) were immediately prepared for analysis, thereby preserving in vivo gene expression and lipid profiles. Macrophages derived from LDLR KO mice fed the HCHF diet contained nearly four-fold more total cholesterol than cells from WT mice fed the same diet. Quantitative analysis of 245 lipid species revealed significant changes in nearly all major lipid classes. Using a two-way ANOVA model, we found that 176 (72%) of the lipids analyzed were significantly affected by the HCHF diet, 133 (54%) by the LDLR KO genotype, and 114 (46%) by interactions between the HCHF diet and LDLR KO genotype. Many of the observed interactions (60%) were synergistic.
INSTITUTE
LIPID MAPS
DEPARTMENT
Multiple
LABORATORY
Multiple
LAST_NAME
Fahy
FIRST_NAME
Eoin
ADDRESS
9500 Gilman, La Jolla, CA, 92093, USA
EMAIL
efahy@ucsd.edu
PHONE
858-534-4076
PUBLICATIONS
Spann NJ, Garmire LX, McDonald JG, Myers DS, Milne SB, Shibata N, Reichart D, Fox JN, Shaked I, Heudobler D, Raetz CR, Wang EW, Kelly SL, Sullards MC, Murphy RC, Merrill AH Jr, Brown HA, Dennis EA, Li AC, Ley K, Tsimikas S, Fahy E, Subramaniam S, Quehenberger O, Russell DW, Glass CK. Regulated accumulation of desmosterol integrates macrophage lipid metabolism and inflammatory responses. Cell. 2012 Sep 28;151(1):138-52. doi: 10.1016/j.cell.2012.06.054. PMID: 23021221; PMCID: PMC3464914.
Estimating Platelet Mitochondrial Function in Patients with Sepsis - Platelet NMRs (part-I)
STUDY_TYPE
single timepoint
STUDY_SUMMARY
Relationships between platelet mitochondrial oxygen consumption rates (mOCR) and metabolites in platelets as measured by quantitative 1H-NMR metabolomics. Samples collected in ED at a single timepoint. WB and platelets isolated from the same blood samples. Comparison of mitochondrial function and metabolomics in patients with sepsis and non-sepsis ED patients
INSTITUTE
University of Michigan, University of Mississippi, University of Minnesota
DEPARTMENT
Clinical Pharmacy (UMich); Emergency Medicine (UMiss)
Estimating Platelet Mitochondrial Function in Patients with Sepsis - WB NMRs (part-II)
STUDY_TYPE
single timepoint
STUDY_SUMMARY
Relationships between platelet mitochondrial oxygen consumption rates (mOCR) and metabolites in platelets as measured by quantitative 1H-NMR metabolomics in WB. Comparison of mitochondrial function and metabolomics in patients with sepsis and non-sepsis ED patients
INSTITUTE
University of Michigan, University of Mississippi, University of Minnesota
DEPARTMENT
Clinical Pharmacy (UMich); Emergency Medicine (UMiss)
Metatranscriptomic Analysis of the Mouse Gut Microbiome Response to the Persistent Organic Pollutant 2,3,7,8-Tetrachlorodibenzofuran
STUDY_SUMMARY
Persistent organic pollutants (POPs) are important environmental chemicals and continued study of their mechanism of action remains a high priority. POPs, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrachlorodibenzofuran (TCDF), and polychlorinated biphenyls (PCBs), are widespread environmental contaminants that are agonists for the aryl hydrocarbon receptor (AHR). Activation of the AHR modulates the gut microbiome community structure and function, host immunity, and the host metabolome. In the current study, male C57BL6/J mice were exposed, via the diet, to 5 ug/kg body weight (BW) TCDF or 24 ug/kg BW of TCDF every day for 5 days. The functional and structural changes imparted by TCDF exposure to the gut microbiome and host metabolome were explored via 16S rRNA gene amplicon sequencing, metabolomics, and bacterial metatranscriptomics. Significant changes included increases in lipopolysaccharide (LPS) biosynthesis gene expression after exposure to 24 ug/kg BW of TCDF. Increases in LPS biosynthesis were confirmed with metabolomics and LPS assays using serum obtained from TCDF-treated mice. Significant increases in gene expression within aspartate and glutamate metabolism were noted after exposure to 24 ug/kg BW of TCDF. Together, these results suggest that after exposure to 24 ug/kg BW of TCDF, the gut microbiome increases the production of LPS and glutamate to promote localized gut inflammation, potentially using glutamate as a stress response.
INSTITUTE
The Pennsylvania State University (Penn State)
LAST_NAME
Nichols
FIRST_NAME
Robert
ADDRESS
917 Old Boalsburg Road, State College, Pennsylvania, 16801, USA
1H NMR metabolomics corroborates serine hydroxymethyltransferase as the primary target of 2-aminoacrylate in a ridA mutant of Salmonella enterica
STUDY_TYPE
NMR metabolomics on Salmonella enterica
STUDY_SUMMARY
The reactive intermediate deaminase RidA (EC: 3.5.99.10) is conserved across all domains of life and deaminates reactive enamine species. When S. enterica ridA mutants are grown in minimal medium, 2-aminoacrylate (2AA) accumulates, damages several pyridoxal 5’-phosphate (PLP)- dependent enzymes, and elicits an observable growth defect. Genetic studies suggested that damage to serine hydroxymethyltransferase (GlyA), and the resultant depletion of 5,10-methelenetetrahydrofolate (5,10-mTHF), was responsible for the observed growth defect. However, the downstream metabolic consequence from GlyA damage by 2AA remains relatively unexplored. This study sought to use untargeted 1H NMR metabolomics to determine whether the metabolic state of a S. enterica ridA mutant was accurately reflected by characterizing growth phenotypes. The data supported the conclusion that metabolic changes in a ridA mutant were due to the IlvA-dependent generation of 2AA, and that the majority of these changes were a consequence of damage to GlyA. While many of the shifts in the metabolome of a ridA mutant could be explained, changes in some metabolites were not easily modeled, suggesting that additional levels of metabolic complexity remain to be unraveled.
INSTITUTE
University of Georgia
DEPARTMENT
Microbiology, Biochemistry, Complex Carbohydrate Research Center
LABORATORY
Edison Lab and Downs lab
LAST_NAME
Gouveia
FIRST_NAME
Goncalo
ADDRESS
315 riverbend road, Complex Carbohydrate Research Centre, ATHENS, GA, 30605, USA
Metabolite expression in liver after early life exposure to an endocrine disruptor at 240 days postnatal (part-I)
STUDY_TYPE
Metabolite expression after chemical exposure versus control.
STUDY_SUMMARY
Our early-life environment has a profound influence on developing organs that impact metabolic function and determines disease susceptibility across the life-course. Using a rat model for exposure to an endocrine disrupting chemical (EDC), we show that early-life exposure causes metabolic dysfunction in adulthood and reprograms histone marks in the developing liver to accelerate acquisition of an adult epigenomic signature. This epigenomic reprogramming persists long after the initial exposure, but many reprogrammed genes remain transcriptionally silent with their impact on metabolism not revealed until a later life exposure to a Western-style diet. Diet-dependent metabolic disruption was largely driven by reprogramming of the Early Growth Response 1 (EGR1) transcriptome and production of metabolites in pathways linked to cholesterol, lipid and one-carbon metabolism. These findings demonstrate the importance of epigenome: environment interactions, which early in life accelerate epigenomic aging, and later in adulthood unlock metabolically restricted epigenetic reprogramming to drive metabolic dysfunction.
Lipid expression in liver after early lifer exposure to an endocrine disruptor at 70 days postnatal in the liver (part-II)
STUDY_TYPE
Lipid expression after chemical exposure versus control
STUDY_SUMMARY
Our early-life environment has a profound influence on developing organs that impact metabolic function and determines disease susceptibility across the life-course. Using a rat model for exposure to an endocrine disrupting chemical (EDC), we show that early-life exposure causes metabolic dysfunction in adulthood and reprograms histone marks in the developing liver to accelerate acquisition of an adult epigenomic signature. This epigenomic reprogramming persists long after the initial exposure, but many reprogrammed genes remain transcriptionally silent with their impact on metabolism not revealed until a later life exposure to a Western-style diet. Diet-dependent metabolic disruption was largely driven by reprogramming of the Early Growth Response 1 (EGR1) transcriptome and production of metabolites in pathways linked to cholesterol, lipid and one-carbon metabolism. These findings demonstrate the importance of epigenome:environment interactions, which early in life accelerate epigenomic aging, and later in adulthood unlock metabolically restricted epigenetic reprogramming to drive metabolic dysfunction.
Lipid expression in serum after early lifer exposure to an endocrine disruptor at 70 days postnatal (part-III)
STUDY_TYPE
Lipid expression after chemical exposure versus control.
STUDY_SUMMARY
Our early-life environment has a profound influence on developing organs that impact metabolic function and determines disease susceptibility across the life-course. Using a rat model for exposure to an endocrine disrupting chemical (EDC), we show that early-life exposure causes metabolic dysfunction in adulthood and reprograms histone marks in the developing liver to accelerate acquisition of an adult epigenomic signature. This epigenomic reprogramming persists long after the initial exposure, but many reprogrammed genes remain transcriptionally silent with their impact on metabolism not revealed until a later life exposure to a Western-style diet. Diet-dependent metabolic disruption was largely driven by reprogramming of the Early Growth Response 1 (EGR1) transcriptome and production of metabolites in pathways linked to cholesterol, lipid and one-carbon metabolism. These findings demonstrate the importance of epigenome:environment interactions, which early in life accelerate epigenomic aging, and later in adulthood unlock metabolically restricted epigenetic reprogramming to drive metabolic dysfunction.
Lipid expression in serum after early life exposure to an endocrine disruptor and a Western Diet at 240 days postnatal (part-IV)
STUDY_TYPE
Lipid expression after chemical exposure versus control
STUDY_SUMMARY
Our early-life environment has a profound influence on developing organs that impact metabolic function and determines disease susceptibility across the life-course. Using a rat model for exposure to an endocrine disrupting chemical (EDC), we show that early-life exposure causes metabolic dysfunction in adulthood and reprograms histone marks in the developing liver to accelerate acquisition of an adult epigenomic signature. This epigenomic reprogramming persists long after the initial exposure, but many reprogrammed genes remain transcriptionally silent with their impact on metabolism not revealed until a later life exposure to a Western-style diet. Diet-dependent metabolic disruption was largely driven by reprogramming of the Early Growth Response 1 (EGR1) transcriptome and production of metabolites in pathways linked to cholesterol, lipid and one-carbon metabolism. These findings demonstrate the importance of epigenome:environment interactions, which early in life accelerate epigenomic aging, and later in adulthood unlock metabolically restricted epigenetic reprogramming to drive metabolic dysfunction.
Retargeting azithromycin-like compounds as antimalarials with dual modality
STUDY_SUMMARY
Resistance to front-line antimalarials (artemisinin combination therapies) is spreading, and development of new drug treatment strategies to rapidly kill Plasmodium parasites that cause malaria are urgently needed. Here, we show that azithromycin—a clinically used macrolide antibiotic that targets the bacterium-like ribosome of the malaria parasites apicoplast organelle and causes a slow-killing ‘delayed death’ phenotype—can also rapidly kill parasites throughout the asexual blood-stages of the lifecycle via a ‘quick-killing’ mechanism of action. Investigation of 84 azithromycin analogues revealed nanomolar quick-killing potency that is directed against the very earliest stage of parasite development within red blood cells. Indeed, the best analogue exhibited 1600-fold higher potency than azithromycin for in vitro treatment windows less than 48 hours. Analogues were also effective against the zoonotic malaria parasite P. knowlesi, and against both multi-drug and artemisinin resistant P. falciparum lines. Metabolomic profiles of azithromycin analogue treated parasites were similar to those of chloroquine treated parasites, suggesting that the quick-killing mechanism of action may in part be localised to the parasite food vacuole. However, metabolomic signatures associated with mitochondrial disruption were also present. In addition, unlike chloroquine, azithromycin and analogues were active across blood stage development, including merozoite invasion, suggesting that these macrolides have a multi-factorial mechanism of quick-killing activity. The positioning of functional groups added to azithromycin and its quick-killing analogues altered their activity against bacterial-like ribosomes but had minimal change on quick-killing activity, which suggests that apicoplast-targeting, delayed-death activity can either be preserved or removed independently of quick-killing. Apicoplast minus parasites remained susceptible to both azithromycin and its analogues, further demonstrating that quick-killing is independent of apicoplast-targeting, delayed-death activity. Therefore, development of azithromycin and analogues as antimalarials offers the possibility of targeting parasites through both a quick-killing and delayed death mechanism of action in a single, multifactorial chemotype.
INSTITUTE
Monash University
LAST_NAME
Siddiqui
FIRST_NAME
Ghizal
ADDRESS
381 Royal Parade, Parkville, Melbourne, Victoria, 3052, Australia
Dynamics of Exposure, Phthalates, and Asthma in a Randomized Trial (DEPART)
STUDY_TYPE
CHEAR Study
STUDY_SUMMARY
project will investigate relationships between phthalate exposure, pediatric asthma health, and underlying biological pathways of toxicity among a rural, underserved Latino population located in Yakima Valley, WA. DEPART will benefit from the original study’s (HAPI’s) robust longitudinal repeat-measure design and community-engaged framework. DEPART will add new measurements including concentrations of urinary phthalate monoester metabolites and biomarkers of oxidative stress to better characterize exposure-response associations. This project’s primary goal is to deepen the understanding of pathophysiological phenomena underlying exposure-response relationships between phthalates and asthma health. Our specific aims are: (1) Characterize associations between urinary phthalate metabolite concentrations and short-term asthma morbidity, and (2) Determine individual relationships between urinary phthalate metabolite concentrations, short-term asthma morbidity, and biomarkers for oxidative stress to assess the potential for a mediating effect by oxidative stress. Covariates of interest will include atopic status, randomized intervention grouping, and the caregiver psychosocial stress assessment.
INSTITUTE
Icahn School of Medicine at Mount Sinai
DEPARTMENT
Department of Environmental Medicine and Public Health
We analyzed mouse serum samples from a mouse dietary intervention experiment. Briefly, C57BL/6 mice (n=44) were divided into 4 groups (n=11 per group) and fed High-fat diet (HFD), 1% deoxycholic acid (DCA) in drinking water, both, or left as control for 9 months. For quality control, 12 TQC samples and 2 blanks were also included in the analysis (total 58 samples and 6 groups). The two treatments were selected to demonstrate the ability of lipidomics to detect gross changes induced by HFD in the serum lipidome, as well as specific/minor changes induced by the secondary bile acid (DCA) through regulation of liver lipid metabolism.
Deadly Duality of PEBP1: Shutting off Necroptosis, Turning on Ferroptosis
STUDY_TYPE
Observation study
STUDY_SUMMARY
Necroptosis and ferroptosis are two pathways of regulated cell death executed in several major cardiovascular and neurological acute and degenerative diseases. While the necroptosis program relies on activation of RIP1, RIP3 kinases and MLKL, ferroptotic death is triggered by 15- Lipoxygenase (15LO) catalyzed oxidation of arachidonoyl- (AA) or adrenoyl- (AdA) phosphatidylethanolamines (PE) controlled by the phosphatidylethanolamine-binding protein 1 (PEBP1). PEBP1 displays “regulatory” promiscuity towards multiple protein partners, including RAF1 kinase. Given a distinct structural homology between RAF1 kinase and RIP3 kinase, we hypothesized that PEBP1 may interact with RIP3 and act as a switch from necroptosis to ferroptosis. Using computational, genetic and redox lipidomics approaches, we show that PEBP1 liberated from RAF1 kinase binds and sterically inhibits RIP3 thus turning-off necroptosis. Highly expressed 15LO may outcompete and bind PEBP1 to promote AA-PE/AdA-PE oxidation and ferroptosis. Using cell- based and animal models, we identified the conditions disrupting PEBP1’s interactions with RAF1 kinase to alternatively bind/inhibit RIP3 kinase or bind/activate 15LO. We further established that PEBP1 knockdown sensitizes cells to RIP3-mediated necroptosis. These newly established regulatory functions of PEBP1 serve multiple and diverse roles across various human disease states.
Effect of high-fat diet and bile acid treatment on serum and tissue lipidomes in mice
STUDY_SUMMARY
We analyzed mouse serum and esophageal tissue samples from a mouse dietary intervention experiment. Briefly, C57BL/6 mice (n=44) were divided into 4 groups (n=11 per group) and fed High-fat diet (HFD), 0.2% deoxycholic acid (DCA) in drinking water, both, or left as control for 9 months. For quality control,TQC samples and blanks were also included in the analysis. The two treatments were selected to demonstrate the ability of lipidomics to detect gross changes induced by HFD in the serum and tissue lipidomes, as well as specific/minor changes induced by the secondary bile acid (DCA) through regulation of liver lipid metabolism. The serum and tissue samples were analyzed using targeted and untargeted lipidomics methods. The targeted serum lipidomics data has previously been uploaded as part of study ST001323.
Serum was processed using a targeted metabolomics platform for quantifying tryptophan metabolites as a number of these metabolites are well establish uremic toxins.
INSTITUTE
University of Florida
LAST_NAME
Ryan
FIRST_NAME
Terence
ADDRESS
1864 Stadium Rd, FLG 114, Gainesville, FL, 32611, USA
Fructosamine-3-kinase (FN3K) KO in HepG2 liver cancer cells
STUDY_SUMMARY
Fructosamine-3-kinases (FN3Ks) are a family of metabolic kinases which are evolutionarily related to eukaryotic protein kinases. Aberrant regulation of these kinases by altered redox homeostasis is a major contributing factor in aging and disease. However, the mechanisms of regulation and cellular functions of these kinases are not known. Bioinformatic analyses of cancer cell lines identified significant overexpression of FN3K in liver and eye cancer cells. To assess the functional significance of this increased expression, a CRISPR knockout of FN3K (FN3K-KO) was generated in the HepG2 liver cancer cell line. The metabolome was compared between FN3K-KO and WT HepG2 cells using untargeted 1H NMR metabolomics. This revealed significant differences in several metabolites that suggest a role for FN3K in regulating redox and energy balance in HepG2 cells.
INSTITUTE
University of Georgia
DEPARTMENT
Complex Carbohydrate Research Center
LABORATORY
Edison
LAST_NAME
Colonna
FIRST_NAME
Maxwell
ADDRESS
315 Riverbend Rd, Athens, GA 30602
EMAIL
maxwellbaca@uga.edu
PHONE
7065420257
NUM_GROUPS
2
PUBLICATIONS
A redox-active switch in Fructosamine-3-kinases expands the regulatory repertoire of the protein kinase super-family
2,3,7,8 -Tetrachlorodibenzo-p-dioxin Mediated Effects on Hepatic Coenzyme A (CoA) and Acetyl-CoA Levels
STUDY_TYPE
Dioxin
STUDY_SUMMARY
Experiment to study TCDD-elicited effects on hepatic Coenzyme A (CoA) and Acetyl-CoA levels in liver of male mice treated with sesame oil vehicle or 0.01-30 ug/kg TCDD every 4 days for 28 days.
Stirred suspension bioreactors maintain naïve pluripotency of human pluripotent stem cells (hPSCs)
STUDY_SUMMARY
Although cell therapies require large numbers of quality-controlled hPSCs, existing technologies are limited in their ability to efficiently grow and scale stem cells. We report here that cell-state conversion from primed-to-naïve pluripotency enhances the biomanufacturing of hPSCs. Naïve hPSCs exhibit superior growth kinetics and aggregate formation characteristics in stirred suspension bioreactors compared to their primed counterparts. Moreover, we demonstrate the role of the bioreactor mechanical environment in the maintenance of naïve pluripotency, through transcriptomic enrichment of mechano-sensing signaling for cells in the bioreactor along with a decrease in expression of lineage-specific and primed pluripotency hallmarks. Bioreactor-cultured, naïve hPSCs express epigenetic regulatory transcripts associated with naïve pluripotency, and display hallmarks of X-chromosome reactivation. They exhibit robust production of naïve pluripotency metabolites and display reduced expression of primed pluripotency cell surface markers. We also show that these cells retain the ability to undergo targeted differentiation into beating cardiomyocytes, hepatocytes, and neural rosettes. They additionally display faster kinetics of teratoma formation compared to their primed counterparts. Naïve bioreactor hPSCs also retain structurally stable chromosomes. Our research corroborates that converting hPSCs to the naïve state enhances hPSC manufacturing and indicates a potentially important role for the bioreactor’s mechanical environment in maintaining naïve pluripotency.
Lipid profile Dataset of optogenetics induced optic nerve regeneration
STUDY_SUMMARY
Using the transgenic Chr2 mouse (Thy1-ChR2-EYFP) as a model of regeneration, we present the profile the lipid changes that occur after optic nerve crush, light stimulation and RGC growth. Thy1-ChR2-EYFP mice and controls (C57BL/6) were divided in four groups each, no crush and no stimulation, no crush and stimulation, crush and no stimulation, crush and stimulation.
Distinct metabolic states of a cell guide alternate fates of mutational buffering through altered proteostasis
STUDY_SUMMARY
Changes in metabolism can alter the cellular milieu; can this also change intracellular proteostasis? Since proteostasis can modulate mutational buffering, if change in metabolism has the ability to change proteostasis, arguably, it should also alter mutational buffering. Building on this, we find that altered cellular metabolic states in E. coli buffer distinct mutations. Buffered-mutants had folding problems in vivo and were differently chaperoned in different metabolic states. Notably, this assistance was dependent upon the metabolites and not on the increase in canonical chaperone machineries. Additionally, we were able to reconstitute the folding assistance afforded by metabolites in vitro and propose that changes in metabolite concentrations have the potential to alter proteostasis. Collectively, we unravel that the metabolite pools are bona fide members of proteostasis and aid in mutational buffering. Given the plasticity in cellular metabolism, we posit that metabolic alterations may play an important role in the positive or negative regulation of proteostasis.
INSTITUTE
CSIR National Chemical Laboratory
LAST_NAME
Shanmugam
FIRST_NAME
Dhanasekaran
ADDRESS
Dr. Homi Bhabha Road, Pune, maharashtra, 411008, India
Compatible solutes were quantified in sea-ice diatoms
STUDY_SUMMARY
Sea-ice algae provide an important source of primary production in polar regions, yet we have limited understanding of their responses to the seasonal cycling of temperature and salinity. Using a targeted liquid chromatography-mass spectrometry-based metabolomics approach, we found that axenic cultures of the Antarctic sea-ice diatom, Nitzschia lecointei, displayed large differences in their metabolomes when grown in a matrix of conditions that included temperatures of –1 and 4°C, and salinities of 32 and 41, despite relatively small changes in growth rate. Temperature exerted a greater effect than salinity on cellular metabolite pool sizes, though the N- or S-containing compatible solutes, 2,3-dihydroxypropane-1-sulfonate (DHPS), glycine betaine (GBT), dimethylsulfoniopropionate (DMSP), and proline responded strongly to both temperature and salinity, suggesting complexity in their control. We saw the largest (> 4 fold) response to salinity for proline. DHPS, a rarely studied but potential compatible solute, reached the highest intracellular compatible solute concentrations of ~ 85 mM. When comparing the culture findings to natural Arctic sea-ice diatom communities, we found extensive overlap in metabolite profiles, highlighting the relevance of culture-based studies to probe environmental questions. Large changes in sea-ice diatom metabolomes and compatible solutes over a seasonal cycle could be significant components of biogeochemical cycling within sea ice.
INSTITUTE
University of Washington
DEPARTMENT
School of Oceanography
LABORATORY
Ingalls Lab
LAST_NAME
Dawson
FIRST_NAME
Hannah
ADDRESS
1501 NE Boat Street, Marine Science Building, Room G, Seattle, WA 98195
Steady-state metabolomics time course of Saccharomyces cerevisiae mitochondrial fatty acid synthesis (mtFAS) mutants
STUDY_TYPE
Steady-state targeted and untargeted metabolomics time course
STUDY_SUMMARY
The goal of this work was to analyze metabolic changes in yeast at various time points with either the oar1 KO or the mct1 knock-out conditions when compared to a time-matched wild-type samples using gas chromatography-mass spectrometry (GC-MS).
INSTITUTE
University of Utah
DEPARTMENT
Biochemistry
LABORATORY
Rutter
LAST_NAME
Berg
FIRST_NAME
Jordan
ADDRESS
15 N Medical Drive East RM 5520, Salt Lake City, UT 84112-5650 USA
Ontogeny related changes in the pediatric liver metabolome
STUDY_SUMMARY
A major challenge in implementing personalized medicine in pediatrics is identifying appropriate drug dosages for children. The majority of drug dosing studies have been based on adult populations, often with modification of the dosing for children based on size and weight. However, the growth and development experienced by children between birth and adulthood represents a dynamically changing biological system, with implications for effective drug dosing, efficacy as well as potential drug toxicity. The purpose of this study was to apply a metabolomics approach to gain preliminary insights into the ontogeny of liver function from newborn to adolescent.
Ontogeny related changes in the pediatric liver metabolome (part-II)
STUDY_SUMMARY
A major challenge in implementing personalized medicine in pediatrics is identifying appropriate drug dosages for children. The majority of drug dosing studies have been based on adult populations, often with modification of the dosing for children based on size and weight. However, the growth and development experienced by children between birth and adulthood represents a dynamically changing biological system, with implications for effective drug dosing, efficacy as well as potential drug toxicity. The purpose of this study was to apply a metabolomics approach to gain preliminary insights into the ontogeny of liver function from newborn to adolescent.
Ontogeny related changes in the pediatric liver metabolome (part-III)
STUDY_SUMMARY
A major challenge in implementing personalized medicine in pediatrics is identifying appropriate drug dosages for children. The majority of drug dosing studies have been based on adult populations, often with modification of the dosing for children based on size and weight. However, the growth and development experienced by children between birth and adulthood represents a dynamically changing biological system, with implications for effective drug dosing, efficacy as well as potential drug toxicity. The purpose of this study was to apply a metabolomics approach to gain preliminary insights into the ontogeny of liver function from newborn to adolescent.
MDM2-Dependent Rewiring of Metabolomic and Lipidomic Profiles in Dedifferentiated Liposarcoma Models
STUDY_SUMMARY
Dedifferentiated liposarcoma (DDLPS) is an aggressive mesenchymal cancer marked by amplification of MDM2, an inhibitor of the tumor suppressor TP53. DDLPS patients with higher MDM2 amplification have lower chemotherapy sensitivity and worse outcome than patients with lower MDM2 amplification. We hypothesized that MDM2 amplification levels may be associated with changes in DDLPS metabolism. Six patient-derived DDLPS cell line models were subject to comprehensive metabolomic (Metabolon) and lipidomic (SCIEX 5600 TripleTOF-MS) profiling to assess associations with MDM2 amplification and their responses to metabolic perturbations. Comparing metabolomic profiles between MDM2 higher and lower amplification cells yielded a total of 23 differentially abundant metabolites across both panels (FDR < 0.05, log2 FC < 0.75), including ceramides, glycosylated ceramides, and sphingomyelins. Disruption of lipid metabolism through statin administration resulted in a chemo-sensitive phenotype in MDM2 lower cell lines only, suggesting that lipid metabolism may be a large contributor to the more aggressive nature of MDM2 higher DDLPS tumors. This study is the first to provide comprehensive metabolomic and lipidomic characterization of DDLPS cell lines and provides evidence for MDM2-dependent differential molecular mechanisms that are critical factors in chemoresistance and could thus affect patient outcome.
Environmental chemical burden in metabolic tissues and systemic biological pathways in adolescent bariatric surgery patients: A pilot untargeted metabolomic approach (part-II)
Background: Advances in untargeted metabolomic technologies have great potential for insight into adverse metabolic effects underlying exposure to environmental chemicals. However, important challenges need to be addressed, including how biological response corresponds to the environmental chemical burden in different target tissues. Aim: We performed a pilot study using state-of-the-art ultra-high-resolution mass spectrometry (UHRMS) to characterize the burden of lipophilic persistent organic pollutants (POPs) in metabolic tissues and associated alterations in the plasma metabolome. Methods: We studied 11 adolescents with severe obesity at the time of bariatric surgery. We measured 18 POPs that can act as endocrine and metabolic disruptors (i.e. 2 dioxins, 11 organochlorine compounds [OCs] and 5 polybrominated diphenyl ethers [PBDEs]) in visceral and subcutaneous abdominal adipose tissue (vAT and sAT), and liver samples using gas chromatography with UHRMS. Biological pathways were evaluated by measuring the plasma metabolome using high-resolution metabolomics. Network and pathway enrichment analysis assessed correlations between the tissue-specific burden of three frequently detected POPs (i.e. p,p’-dichlorodiphenyldichloroethene [DDE], hexachlorobenzene [HCB] and PBDE-47) and plasma metabolic pathways. Results: Concentrations of 4 OCs and 3 PBDEs were quantifiable in at least one metabolic tissue for >80% of participants. All POPs had the highest median concentrations in adipose tissue, especially sAT, except for PBDE-154, which had comparable average concentrations across all tissues. Pathway analysis showed high correlations between tissue-specific POPs and metabolic alterations in pathways of amino acid metabolism, lipid and fatty acid metabolism, and carbohydrate metabolism. Conclusions: Most of the measured POPs appear to accumulate preferentially in adipose tissue compared to liver. Findings of plasma metabolic pathways potentially associated with tissue-specific POPs concentrations merit further investigation in larger populations.
INSTITUTE
Icahn School of Medicine at Mount Sinai
DEPARTMENT
Environmental Medicine and Public Health
LABORATORY
High Resolution Exposomics Research Group
LAST_NAME
Walker
FIRST_NAME
Doug
ADDRESS
One Gustave L. Levy Place, Box 1057, New York, NY 10029
EMAIL
douglas.walker@mssm.edu
PHONE
212-241-9891
NUM_GROUPS
4
TOTAL_SUBJECTS
11
NUM_MALES
1
NUM_FEMALES
10
STUDY_COMMENTS
Upload #1: Visceral and subcutaneous abdominal adipose tissue, liver tissue. Plasma metabolomics are in upload #2
PUBLICATIONS
Valvi D, Walker DI, Inge T, Bartell SM, Jenkins T, Helmrath M, Ziegler TR, La Merrill MA, Eckel SP, Conti D, Liang Y, Jones DP, McConnell R, Chatzi L. (2020). Environmental chemical burden in metabolic tissues and systemic biological pathways in adolescent bariatric surgery patients: A pilot untargeted metabolomic approach. Environment International. In Press.
Environmental chemical burden in metabolic tissues and systemic biological pathways in adolescent bariatric surgery patients: A pilot untargeted metabolomic approach
Background: Advances in untargeted metabolomic technologies have great potential for insight into adverse metabolic effects underlying exposure to environmental chemicals. However, important challenges need to be addressed, including how biological response corresponds to the environmental chemical burden in different target tissues. Aim: We performed a pilot study using state-of-the-art ultra-high-resolution mass spectrometry (UHRMS) to characterize the burden of lipophilic persistent organic pollutants (POPs) in metabolic tissues and associated alterations in the plasma metabolome. Methods: We studied 11 adolescents with severe obesity at the time of bariatric surgery. We measured 18 POPs that can act as endocrine and metabolic disruptors (i.e. 2 dioxins, 11 organochlorine compounds [OCs] and 5 polybrominated diphenyl ethers [PBDEs]) in visceral and subcutaneous abdominal adipose tissue (vAT and sAT), and liver samples using gas chromatography with UHRMS. Biological pathways were evaluated by measuring the plasma metabolome using high-resolution metabolomics. Network and pathway enrichment analysis assessed correlations between the tissue-specific burden of three frequently detected POPs (i.e. p,p’-dichlorodiphenyldichloroethene [DDE], hexachlorobenzene [HCB] and PBDE-47) and plasma metabolic pathways. Results: Concentrations of 4 OCs and 3 PBDEs were quantifiable in at least one metabolic tissue for >80% of participants. All POPs had the highest median concentrations in adipose tissue, especially sAT, except for PBDE-154, which had comparable average concentrations across all tissues. Pathway analysis showed high correlations between tissue-specific POPs and metabolic alterations in pathways of amino acid metabolism, lipid and fatty acid metabolism, and carbohydrate metabolism. Conclusions: Most of the measured POPs appear to accumulate preferentially in adipose tissue compared to liver. Findings of plasma metabolic pathways potentially associated with tissue-specific POPs concentrations merit further investigation in larger populations.
INSTITUTE
Icahn School of Medicine at Mount Sinai
DEPARTMENT
Environmental Medicine and Public Health
LABORATORY
High Resolution Exposomics Research Group
LAST_NAME
Walker
FIRST_NAME
Doug
ADDRESS
One Gustave L. Levy Place, Box 1057, New York, NY 10029
EMAIL
douglas.walker@mssm.edu
PHONE
212-241-9891
NUM_GROUPS
1
TOTAL_SUBJECTS
11
NUM_MALES
1
NUM_FEMALES
10
STUDY_COMMENTS
Upload #1: Visceral and subcutaneous abdominal adipose tissue, liver tissue. Plasma metabolomics are in upload #2
PUBLICATIONS
Valvi D, Walker DI, Inge T, Bartell SM, Jenkins T, Helmrath M, Ziegler TR, La Merrill MA, Eckel SP, Conti D, Liang Y, Jones DP, McConnell R, Chatzi L. (2020). Environmental chemical burden in metabolic tissues and systemic biological pathways in adolescent bariatric surgery patients: A pilot untargeted metabolomic approach. Environment International. In Press.
ANALYSIS_TYPE_DETAIL
LC-HRMS untargeted metabolomic profiling of plasma
Patterns in metabolite pools show that phytoplankton leave a taxon-specific signature on particulate carbon: Surface samples from the North Pacific Subtropical Gyre to North Pacific Transition Zone
STUDY_TYPE
Marine metabolomics surface samples from the North Pacific Subtropical Gyre to North Pacific Transition Zone
STUDY_SUMMARY
In the surface ocean, carbon is fixed by phytoplankton and respired by the entire marine community at an astonishingly high rate. At any point in time, the difference between these two processes yields a carbon pool in surface particles that is a combination of both freshly fixed and partially degraded material. On a molecular level, we have a limited knowledge of the small molecules, or metabolites, within this pool. Specific metabolites have been shown to be responsible for fueling respiration, maintaining organismal interactions, and transferring energy throughout the microbial community. Metabolomics, or the direct observation and quantification of the small molecules that are the result of cellular activity, provides an important lens through which we can begin to assess the standing stocks of small compounds that likely fuel a great deal of heterotrophic activity in the surface ocean. Here we describe community metabolomes of particulate material into the North Pacific Ocean and compare the metabolomes to a variety of phytoplankton grown in the lab. Using both targeted and untargeted metabolomics, we identify metabolites in the particulate carbon pool and explore their latitudinal and phylogenetic distributions. This analysis reveals several compounds that have not been previously recognized as abundant components of the marine organic carbon pool. We found that the community metabolome showed distinct differences between the regimes that likely reflects the phytoplankton community present. The community metabolome in surface waters of the subtropical domain was remarkably consistent even when sampled weeks apart, while the northern regions showed a patchier and less reproducible community metabolome. Some individual compounds showed distinct patterns between oceanographic regimes, including homarine, an abundant molecule that can contribute up to 4% of the total particulate carbon pool in marine surface waters. Glutamic acid and glutamine showed opposite patterns in the oceanographic regimes, suggesting differences in community-level nitrogen assimilation in these different regimes. Overall, this study offers a new perspective into particulate carbon composition in oceanographic research, reveals important carbon pools that may fuel the microbial loop, and suggests an altered community-level nitrogen assimilation capacity over the North Pacific transition zone.
INSTITUTE
University of Washington
DEPARTMENT
School of Oceanography
LABORATORY
Ingalls Lab
LAST_NAME
Heal
FIRST_NAME
Katherine
ADDRESS
1501 NE Boat Street, Marine Science Building, Room G, Seattle, WA, 98195, USA
Metabolomics study in Plasma of Obese Patients with Neuropathy Identifies Potential Metabolomics Signatures
STUDY_SUMMARY
The goal of this study was to characterize biochemical profiles observed in human plasma samples originating from an obese cohort stratified by a diagnosis of neuropathy as well as a cohort of lean control subjects without a clinical manifestation of neuropathy.
INSTITUTE
University of Michigan
LAST_NAME
Feldman
FIRST_NAME
Eva
ADDRESS
5017 AATBSRB, 109 Zina Pitcher Place Ann Arbor, MI 48109-2200
Aspirin Metabolomics in Colorectal Cancer Chemoprevention - blood (part-II)
STUDY_SUMMARY
Substantial evidence supports the effectiveness of aspirin for cancer chemoprevention in addition to its well established role in cardiovascular protection. In recent meta-analyses of randomized controlled trials in human, daily aspirin use reduced incidence, metastasis and mortality from several common types of cancer, especially colorectal cancer. The mechanism(s) by which aspirin exerts an anticancer benefit is uncertain; numerous effects have been described involving both cyclooxygenase-dependent and -independent pathways. The goal of this research is to elucidate the key metabolic changes that are responsible for the anticancer effects of aspirin in humans using untargeted metabolomics analysis. Metabolomics, or global metabolite profiling, is an emerging discipline that has the potential to transform the study of pharmaceutical agents. Our innovative approach will use high-resolution mass spectroscopy to detect thousands of metabolites in blood plasma that were collected from participants in the Aspirin/Folate Polyp Prevention Study, a randomized, double-blind, placebo-controlled trial of aspirin for the prevention of colorectal adenomas. Participants in the trial were assigned with equal probability to three aspirin treatment arms (placebo, 81mg, or 325mg daily). Over the three-year period, 81mg/day of aspirin reduced the risk of adenomas, whereas the 325 mg/day dose had less effect. The aims of the current proposal are to identify metabolomic signatures, including specific metabolites and metabolic pathways, that are associated with aspirin treatment in blood of participants after three years of randomized aspirin treatment; and then to assess the associations of these metabolic signatures with adenoma risk and whether they mediate the reductions in risk due to 81 mg/day aspirin treatment. We will prioritize metabolites for study by evaluating metabolite levels in patients from the placebo and treatment arms while controlling the false discovery rate, use correlation analysis to enhance identification of relevant metabolic modules associated with these prioritized metabolites, and apply pathway mapping with post-hoc application of ion dissociation spectroscopy to representative metabolites to confirm pathway identification. Because aspirin is a multifunctional drug that is thought to modify numerous pathways with potential roles in carcinogenesis, a global discovery-based metabolomics approach is the best way to identify its key activities. The public health significance of this work is substantial because understanding the mechanism of aspirin's anticancer effects is key to optimizing its use and to the development of novel drugs targeting the metabolic pathways identified.
Aspirin Metabolomics in Colorectal Cancer Chemoprevention - blood (part-II)
STUDY_SUMMARY
Substantial evidence supports the effectiveness of aspirin for cancer chemoprevention in addition to its well established role in cardiovascular protection. In recent meta-analyses of randomized controlled trials in human, daily aspirin use reduced incidence, metastasis and mortality from several common types of cancer, especially colorectal cancer. The mechanism(s) by which aspirin exerts an anticancer benefit is uncertain; numerous effects have been described involving both cyclooxygenase-dependent and -independent pathways. The goal of this research is to elucidate the key metabolic changes that are responsible for the anticancer effects of aspirin in humans using untargeted metabolomics analysis. Metabolomics, or global metabolite profiling, is an emerging discipline that has the potential to transform the study of pharmaceutical agents. Our innovative approach will use high-resolution mass spectroscopy to detect thousands of metabolites in blood plasma that were collected from participants in the Aspirin/Folate Polyp Prevention Study, a randomized, double-blind, placebo-controlled trial of aspirin for the prevention of colorectal adenomas. Participants in the trial were assigned with equal probability to three aspirin treatment arms (placebo, 81mg, or 325mg daily). Over the three-year period, 81mg/day of aspirin reduced the risk of adenomas, whereas the 325 mg/day dose had less effect. The aims of the current proposal are to identify metabolomic signatures, including specific metabolites and metabolic pathways, that are associated with aspirin treatment in blood after three years of randomized aspirin treatment; and then to assess the associations of these metabolic signatures with adenoma risk and whether they mediate the reductions in risk due to 81 mg/day aspirin treatment. We will prioritize metabolites for study by evaluating metabolite levels in patients from the placebo and treatment arms while controlling the false discovery rate, use correlation analysis to enhance identification of relevant metabolic modules associated with these prioritized metabolites, and apply pathway mapping with post-hoc application of ion dissociation spectroscopy to representative metabolites to confirm pathway identification. Because aspirin is a multifunctional drug that is thought to modify numerous pathways with potential roles in carcinogenesis, a global discovery-based metabolomics approach is the best way to identify its key activities. The public health significance of this work is substantial because understanding the mechanism of aspirin's anticancer effects is key to optimizing its use and to the development of novel drugs targeting the metabolic pathways identified.
Dependence of the Staphylococcal Volatilome Composition on Microbial Nutrition
STUDY_TYPE
Untargeted MS
STUDY_SUMMARY
Introduction: In vitro cultivation of staphylococci is fundamental to both clinical and research microbiology, and selection of growth medium will substantially influence staph growth rates, genetic integrity, pathogenicity, and metabolic capacity. Few studies, to-date, have investigated how the differences in rich media can influence the volatilome of cultivated bacteria. Objectives: The objective of this study was to determine the influence of rich media composition on the chemical characteristics of the volatilomes of Staphylococcus aureus and S. epidermidis. Methods: S. aureus (ATCC 12600) and S. epidermidis (ATCC 12228) were cultured in triplicate in four rich complex media (BHI, LB, MHB, and TSB), and the volatile metabolites produced by each culture were analyzed using headspace solid-phase microextraction combined with comprehensive two-dimensional gas chromatography – time-of-flight mass spectrometry (HS-SPME-GC×GC-TOFMS). Results: When comparing the chemical compositions of the staph volatilomes produced in each medium, we observed few differences when the presence versus absence of volatiles were compared. However, when the relative abundances of volatiles were included in the analyses, we observed that culturing staph in media containing free glucose (BHI and TSB) resulted in volatilomes dominated by acids and esters (67%). The low-glucose media (LB and MHB) produced ketones in greatest relative abundances, but the volatilome compositions in these two media were highly dissimilar. Conclusion: The staphylococcal volatilome is strongly influenced by the nutritional composition of the growth medium, especially the availability of free glucose, which is much more evident when the relative abundances of the volatiles are analyzed, compared to the presence versus absence.
INSTITUTE
Arizona State University
DEPARTMENT
School of Life Sciences
LABORATORY
Heather D. Bean Lab
LAST_NAME
Bean, Ph.D.
FIRST_NAME
Heather
ADDRESS
PO Box 874501 Tempe, AZ 85287
EMAIL
heather.d.bean@asu.edu
PHONE
4807273395
STUDY_COMMENTS
Staphylococcus aureus (ATCC 12600) and Stpahylococcus epidermidis (ATCC 12228) grown in four complex media
PUBLICATIONS
Jenkins, C. L., H. D. Bean (2020). Influence of media on the differentiation of Staphylococcus spp. by volatile compounds. Journal of breath research 14, 016007 doi:10.1088/1752-7163/ab3e9d
A Compromised Developmental Trajectory of the Infant Gut Microbiome and Metabolome in Atopic Eczema - (untargeted global metabolomics profiling) )
STUDY_SUMMARY
Evidence is accumulating that the establishment of the gut microbiome in early life influences the development of atopic eczema. In this longitudinal study, we used integrated multi-omics analyses to infer functional mechanisms by which the microbiome modulates atopic eczema risk.
INSTITUTE
National University of Singapore (NUS)
LAST_NAME
Ta
FIRST_NAME
Le Duc Huy
ADDRESS
MD1 - Tahir Foundation Building (MD1), Level 15, Department of Paediatrics, Allergy & Immunology Division, National University of Singapore (NUS), 12 Science Drive 2. Singapore 117549
Sap samples from sugar maple trees across the Canadian province of Ontario were collected in 2019. These samples were minimally prepared and analyzed in both positive ESI and negative ESI by C18 and HILIC chromatography. This was done to uncover the chemical changes that occurred in the sap over the season. This will serve as the base for future analysis of maple syrup where compounds that may be responsible for specific organoleptic properties can be linked back to precursors found here in the sap.
7 control fibroblasts samples and 7 patient-derived fibroblasts samples were collected at day 0 and day 5. Intracellular metabolites were extracted from cells cultured in 6 well plate while acyl-CoA and 5-methyltetrahydrofolate were extracted from cells cultured in 60 mm dish.
Metabolomics of lung injury after allogeneic hematopoietic cell transplantation - Colon NMR 1D
STUDY_TYPE
preliminary data
STUDY_SUMMARY
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment option for a variety of hematological malignancies. Interactions between the donor immune system and the patient tissue result in a disease, called GVHD. The pathophysiology of acute GVHD can be hypothesized in three sequential phases: cytokine storm and activation of the antigen-presenting cells (APC), donor T cell activation and effector cell phase. Idiopathic pneumonia syndrome (IPS) is one of the most deleterious complications after allogeneic HCT and is considered not only to be related to conditioning regimen toxicity but also represents an end organ damage caused by allo-reactive T cells, therefore making the lung susceptible to a two-pronged attack, one of which overlaps with GVHD causing other target organ injury. IPS results in mortality of up to 90% of patients. We will use a murine model of IPS and GVHD which is well established in our group, and in which disease evolves either across disparities in major histocompatibility complex (MCH) class I and II, minor histocompatibility antigens (miHags) or both. Metabolomics changes following syngeneic and allogeneic HCT at post-transplantation Days +7 (cytokine storm phase) and Days +42 (cellular effector phase) are compared to baseline wild-type (naive) controls. Prior to analysis, naïve - and experimental mice (N=3 from each group) were fed with semi-liquid diet supplemented with tracers (13C6-glucose ) over 24 hours. At the end of 7 days or 42 days, respectively, feces and aGVHD target organs (colon, liver and lung) were collected from all groups and further processed and / or analyzed. We expect to reveal metabolic pathways affected after allo-HCT which contribute to immune cell mediated lung injury (IPS) and will potentially identify different metabolic pathways in other GVHD target organs.
INSTITUTE
University of Kentucky
DEPARTMENT
MCC
LAST_NAME
Hildebrandt
FIRST_NAME
Gerhard
ADDRESS
CTW-453, 900 South Limestone street. UKY. Lexington, Kentucky-40536
Metabolomics of lung injury after allogeneic hematopoietic cell transplantation - Colon NMR HSQC
STUDY_TYPE
preliminary data
STUDY_SUMMARY
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment option for a variety of hematological malignancies. Interactions between the donor immune system and the patient tissue result in a disease, called GVHD. The pathophysiology of acute GVHD can be hypothesized in three sequential phases: cytokine storm and activation of the antigen-presenting cells (APC), donor T cell activation and effector cell phase. Idiopathic pneumonia syndrome (IPS) is one of the most deleterious complications after allogeneic HCT and is considered not only to be related to conditioning regimen toxicity but also represents an end organ damage caused by allo-reactive T cells, therefore making the lung susceptible to a two-pronged attack, one of which overlaps with GVHD causing other target organ injury. IPS results in mortality of up to 90% of patients. We will use a murine model of IPS and GVHD which is well established in our group, and in which disease evolves either across disparities in major histocompatibility complex (MCH) class I and II, minor histocompatibility antigens (miHags) or both. Metabolomics changes following syngeneic and allogeneic HCT at post-transplantation Days +7 (cytokine storm phase) and Days +42 (cellular effector phase) are compared to baseline wild-type (naive) controls. Prior to analysis, naïve - and experimental mice (N=3 from each group) were fed with semi-liquid diet supplemented with tracers (13C6-glucose ) over 24 hours. At the end of 7 days or 42 days, respectively, feces and aGVHD target organs (colon, liver and lung) were collected from all groups and further processed and / or analyzed. We expect to reveal metabolic pathways affected after allo-HCT which contribute to immune cell mediated lung injury (IPS) and will potentially identify different metabolic pathways in other GVHD target organs.
INSTITUTE
University of Kentucky
DEPARTMENT
MCC
LAST_NAME
Hildebrandt
FIRST_NAME
Gerhard
ADDRESS
CTW-453, 900 South Limestone street. UKY. Lexington, Kentucky-40536
Metabolomics of lung injury after allogeneic hematopoietic cell transplantation - Colon DI-FTMS
STUDY_TYPE
preliminary data
STUDY_SUMMARY
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment option for a variety of hematological malignancies. Interactions between the donor immune system and the patient tissue result in a disease, called GVHD. The pathophysiology of acute GVHD can be hypothesized in three sequential phases: cytokine storm and activation of the antigen-presenting cells (APC), donor T cell activation and effector cell phase. Idiopathic pneumonia syndrome (IPS) is one of the most deleterious complications after allogeneic HCT and is considered not only to be related to conditioning regimen toxicity but also represents an end organ damage caused by allo-reactive T cells, therefore making the lung susceptible to a two-pronged attack, one of which overlaps with GVHD causing other target organ injury. IPS results in mortality of up to 90% of patients. We will use a murine model of IPS and GVHD which is well established in our group, and in which disease evolves either across disparities in major histocompatibility complex (MCH) class I and II, minor histocompatibility antigens (miHags) or both. Metabolomics changes following syngeneic and allogeneic HCT at post-transplantation Days +7 (cytokine storm phase) and Days +42 (cellular effector phase) are compared to baseline wild-type (naive) controls. Prior to analysis, naïve - and experimental mice (N=3 from each group) were fed with semi-liquid diet supplemented with tracers (13C6-glucose ) over 24 hours. At the end of 7 days or 42 days, respectively, feces and aGVHD target organs (colon, liver and lung) were collected from all groups and further processed and / or analyzed. We expect to reveal metabolic pathways affected after allo-HCT which contribute to immune cell mediated lung injury (IPS) and will potentially identify different metabolic pathways in other GVHD target organs.
INSTITUTE
University of Kentucky
DEPARTMENT
MCC
LAST_NAME
Hildebrandt
FIRST_NAME
Gerhard
ADDRESS
CTW-453, 900 South Limestone street. UKY. Lexington, Kentucky-40536
Quantification of lipid species from cultured human MDA-MB-231 and BT549 cells with or without siRNA knockdown of ACSL1 and treated or not with eleostearic acid
Metabolites changes related to glucose-mediated energy production in chemotheraphy-induced cachexia
STUDY_SUMMARY
Targeted metabolomics platforms included amino acids and metabolites related to glucose-mediated energy production. The targeted metabolome changed with chemotheraphy-induced cachexia, and the changes were reversed with potential treatment of the cachexia. .rdb files were included as raw data files where detailed information regarding MRM transitions and internal standards can be found. Several amino acids (Gly, Pro, Gln, Taurine) were analyzed after dilution because their peak intensities were too high. Thus their analysis was performed separately from other amino acids, and their rdb files were saved in separate rdb files.
INSTITUTE
Asan medical Center, University of Ulsan College of Medicine
LAST_NAME
Yoo
FIRST_NAME
Hyun Ju
ADDRESS
88, Olympic-ro, 43-gil, Songpa-gu, Seoul 05505, South Korea
Metabolomics of lung injury after allogeneic hematopoietic cell transplantation - Small Intenstines NMR HSQC
STUDY_TYPE
preliminary data
STUDY_SUMMARY
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment option for a variety of hematological malignancies. Interactions between the donor immune system and the patient tissue result in a disease, called GVHD. The pathophysiology of acute GVHD can be hypothesized in three sequential phases: cytokine storm and activation of the antigen-presenting cells (APC), donor T cell activation and effector cell phase. Idiopathic pneumonia syndrome (IPS) is one of the most deleterious complications after allogeneic HCT and is considered not only to be related to conditioning regimen toxicity but also represents an end organ damage caused by allo-reactive T cells, therefore making the lung susceptible to a two-pronged attack, one of which overlaps with GVHD causing other target organ injury. IPS results in mortality of up to 90% of patients. We will use a murine model of IPS and GVHD which is well established in our group, and in which disease evolves either across disparities in major histocompatibility complex (MCH) class I and II, minor histocompatibility antigens (miHags) or both. Metabolomics changes following syngeneic and allogeneic HCT at post-transplantation Days +7 (cytokine storm phase) and Days +42 (cellular effector phase) are compared to baseline wild-type (naive) controls. Prior to analysis, naïve - and experimental mice (N=3 from each group) were fed with semi-liquid diet supplemented with tracers (13C6-glucose ) over 24 hours. At the end of 7 days or 42 days, respectively, feces and aGVHD target organs (colon, liver and lung) were collected from all groups and further processed and / or analyzed. We expect to reveal metabolic pathways affected after allo-HCT which contribute to immune cell mediated lung injury (IPS) and will potentially identify different metabolic pathways in other GVHD target organs.
INSTITUTE
University of Kentucky
DEPARTMENT
MCC
LAST_NAME
Hildebrandt
FIRST_NAME
Gerhard
ADDRESS
CTW-453, 900 South Limestone street. UKY. Lexington, Kentucky-40536
Design of Experiments for Maximizing T cell endpoints
STUDY_SUMMARY
Purified T cells from a single healthy donor were expanded in vitro with either magnetic beads or degradable micro-scaffold (DMS) particles. Magnetic bead cultures were expanded according to manufacturer’s instructions, while DMS cultures were expanded with varying DMS particle concentration, IL2 concentration, and antigen surface density on the particles, according to a design of experiments. Media of each culture of was sampled repeatedly over the course of a 14 day period. Quantities and characteristics of activated T cells were assessed at the end of the culture period, and media was analyzed by 1H-NMR. Analysis of spectra resulted in a set of 20 features that was used in predictive modeling of T cell endpoints, along with culture parameters described above and cytokine data. A second validation experiment was performed with different values for culture parameters, using the same culture, sampling, and NMR analysis methods.
Lipidomics dataset of PTEN deletion-induced nerve regeneration mouse model
STUDY_SUMMARY
We present the lipidome of adult PTENloxP/loxP mice subjected to intravitreal injection of adeno-associated viruses expressing Cre (AAV-Cre) as a model of regeneration. At 4-week-old, PTENloxP/loxP mice were intravitreally-injected with 2-3 μl of either AAV-Cre (KO) or AAV-PLAP (control), and two weeks later optic nerve crush was performed. At indicated time-points after crush (0 days, 7 days, 14 days), mice were euthanized and optic nerves were immediately dissected out, and then flash frozen on dry ice. The Bligh and Dyer method was used for lipid extraction, followed by mass spectrometry lipid profiling with a Q-Exactive Orbitrap Liquid Chromatography-Mass Spectrometer (LC MS-MS). The raw scans were analysed with LipidSearch 4.2 and the statistical analysis was conducted through Metaboanalyst 4.0
Hepatic [U-13C]Lactate tracing and metabolomics in young and old WT and SIRT6 overexpressing mice
STUDY_SUMMARY
Our previous data had suggested that gluconeogenesis capacity from the precursors lactate and glycerol declines in old C57BL/6 mice. This decline was rescued by whole body SIRT6 overexpression. Since the liver is the main gluconeogenic organ, we performed here liver metabolomics in young (6 months) versus old (20-24 months) WT and SIRT6-transgenic mice. We used liver tissues of 6h morning-fasted mice, either in naïve state or 15 minutes after intraperitoneal injection of 1mg/kg [U-13C]Lactate.
INSTITUTE
Bar Ilan University
DEPARTMENT
The Mina & Everard Goodman Faculty of Life Sciences
Liver metabolomics in old liver-specific SIRT6 overexpressing mice
STUDY_SUMMARY
Our previous data had suggested that gluconeogenesis capacity from the precursors lactate and glycerol declines in old C57BL/6 mice. This decline was rescued by whole body SIRT6 overexpression, but not in liver-specific SIRT6 overexpression. Here we preformed liver metabolomics in old liver-specific SIRT6 overexpression and control mice.
INSTITUTE
Bar Ilan University
DEPARTMENT
The Mina & Everard Goodman Faculty of Life Sciences
Diel investments in phytoplankton metabolite production influenced by associated heterotrophic bacteria
STUDY_TYPE
Incubation experiment
STUDY_SUMMARY
Organic substrate transfer between photoautotrophic and heterotrophic microbes in the surface ocean is a central but poorly understood process in the global carbon cycle. This study developed a co-culture system of marine diatom Thalassiosira pseudonana and heterotrophic bacterium Ruegeria pomeroyi, and addressed diel changes in phytoplankton endometabolite production using nuclear magnetic resonance (NMR) and bacterial metabolite consumption using gene expression. Here we deposit data for NMR analysis from the study. Samples were collected every 6 hours over two days under a diel light cycle. During the course of the study, we observed an increase in some phytoplankton endometabolites presumably due to the effects of the associated bacteria. We introduced an additional experiment and tested this possibility by comparing phytoplankton endometabolite accumulation between axenic treatments and bacteria coculture treatments.
INSTITUTE
University of Georgia
DEPARTMENT
Department of Marine Sciences; Complex Carbohydrate Research Center
Metabolome analysis in the diagnosis of childhood cerebellar ataxia
STUDY_SUMMARY
Metabolome studies to aid in the diagnosis and molecular elucidation of a child presenting chronic progressive cerebellar ataxia and an undiagnosed condition.
INSTITUTE
CEMBIO
LAST_NAME
Sáiz
FIRST_NAME
Jorge
ADDRESS
km 0, Universidad CEU-San Pablo Urbanización Montepríncipe. M-501, 28925 Alcorcón
Stool metabolites of known identity profiled using hybrid nontargeted methods (part-I)
STUDY_SUMMARY
We determined the effect of diet on the composition and metabolic function of human gut microbiome using a controlled feeding experiment with three divergent diets (vegan, omnivore, and an exclusive enteral nutrition diet (EEN) devoid of dietary fiber) in the Food And Resulting Microbial Metabolites (FARMM) study. The study included an antibiotic and polyethylene glycol (Abx/PEG) intervention to dynamically assess the effect of diet on the reconstitution of the gut microbiota and its associated fecal and plasma metabolome. Samples from thirty healthy volunteers between the ages of 18 and 60, 10 mper diet group were analyzed. Self-reported vegans were required to have followed a vegan diet for a minimum of 6 months prior to enrollment. Key exclusion criteria included inflammatory bowel disease, celiac disease, or other chronic intestinal disorders; prior bowel resection surgery other than appendectomy; baseline bowel frequency less than every 2 days or greater than 3 times daily; creatinine concentration greater than the upper limit of normal; diabetes mellitus; currently smoking; body mass index (BMI) <18.5 or >35; and use of antibiotics and probiotics in the prior 6 months. The 10 vegans continued to follow their usual diet as outpatients. All participants completed the Diet History Questionnaire II (DHQ II), a food frequency questionnaire developed by the Risk Factor Monitoring and Methods Branch of the National Cancer Institute. The vegan participants also completed three 24 hour diet recalls with a dietitian in the week prior to starting antibiotics. We randomly assigned the 20 omnivores to receive an omnivore diet or EEN (Modulen® IBD) while residing in an inpatient research unit. The macronutrient composition of Modulen® is protein 36g, fat 47g, and carbohydrate 110g per 1000 Kcal. The two omnivore diets were engineered to have a similar composition to EEN. All the subjects consumed the menu A on day 11 and menu B on days 4 and 14. Diets for omnivores were constructed to provide the expected total calories required per day for the participant to maintain their current weight and were adjusted if there was weight gain or loss of more than 2.5 pounds. On days 6, 7, and 8, inpatients participants received vancomycin 500mg orally every 6 hours and neomycin 1000mg orally every 6 hours. On day 7, participants consumed 4L of polyethylene glycol (PEG) based bowel purgative (GoLytely®). Participants in the omnivore and EEN arms left the inpatient research unit only under the direct supervision of a research staff member. The vegan outpatients reported to the hospital twice on days 6,7 and 8 to receive antibiotics and to consume PEG on day 7. The first stool sample of each day of the inpatient groups was collected, aliquoted and frozen immediately at -80oC. Blood was collected on days 1, 5, 9, 12 and 15 from which plasma aliquots were immediately isolated and frozen at -80oC. The outpatient participants following the vegan diet also had blood collected on days 1, 5, 9, 12, and 15 from which plasma aliquots were immediately isolated and frozen at -80oC. Among these participants, the first stool of the day was collected at home daily and kept on ice packs until it was brought to the research unit where it could be aliquoted and frozen. Samples from vegans were received for aliquoting within 24 hours and on average within 4 hours (Wu et al., 2010). Day 0 stool was not collected from vegans since their diet did not change. The aliquoted amounts for all samples ranged from 500 mg to 1 g. The aliquots were taken from different areas of the sample. Remaining sample was then collected into one residual 50 ml conical tube with a tongue depressor. Any remaining stool was discarded. The University of Pennsylvania Institutional Review Board (IRB) approved the research protocol.
INSTITUTE
Broad Institute of MIT and Harvard
LAST_NAME
Clish
FIRST_NAME
Clary
ADDRESS
415 Main Street, Cambridge, MA, 02142, USA
EMAIL
clary@broadinstitute.org
PHONE
617-714-7654
NUM_GROUPS
3
TOTAL_SUBJECTS
30
NUM_MALES
20
NUM_FEMALES
10
STUDY_COMMENTS
stool samples collected at baseline and 3-4 timepoints
Plasma metabolites of known identity profiled using hybrid nontargeted methods (part-III)
STUDY_SUMMARY
We determined the effect of diet on the composition and metabolic function of human gut microbiome using a controlled feeding experiment with three divergent diets (vegan, omnivore, and an exclusive enteral nutrition diet (EEN) devoid of dietary fiber) in the Food And Resulting Microbial Metabolites (FARMM) study. The study included an antibiotic and polyethylene glycol (Abx/PEG) intervention to dynamically assess the effect of diet on the reconstitution of the gut microbiota and its associated fecal and plasma metabolome. Samples from thirty healthy volunteers between the ages of 18 and 60, 10 mper diet group were analyzed. Self-reported vegans were required to have followed a vegan diet for a minimum of 6 months prior to enrollment. Key exclusion criteria included inflammatory bowel disease, celiac disease, or other chronic intestinal disorders; prior bowel resection surgery other than appendectomy; baseline bowel frequency less than every 2 days or greater than 3 times daily; creatinine concentration greater than the upper limit of normal; diabetes mellitus; currently smoking; body mass index (BMI) <18.5 or >35; and use of antibiotics and probiotics in the prior 6 months. The 10 vegans continued to follow their usual diet as outpatients. All participants completed the Diet History Questionnaire II (DHQ II), a food frequency questionnaire developed by the Risk Factor Monitoring and Methods Branch of the National Cancer Institute. The vegan participants also completed three 24 hour diet recalls with a dietitian in the week prior to starting antibiotics. We randomly assigned the 20 omnivores to receive an omnivore diet or EEN (Modulen® IBD) while residing in an inpatient research unit. The macronutrient composition of Modulen® is protein 36g, fat 47g, and carbohydrate 110g per 1000 Kcal. The two omnivore diets were engineered to have a similar composition to EEN. All the subjects consumed the menu A on day 11 and menu B on days 4 and 14. Diets for omnivores were constructed to provide the expected total calories required per day for the participant to maintain their current weight and were adjusted if there was weight gain or loss of more than 2.5 pounds. On days 6, 7, and 8, inpatients participants received vancomycin 500mg orally every 6 hours and neomycin 1000mg orally every 6 hours. On day 7, participants consumed 4L of polyethylene glycol (PEG) based bowel purgative (GoLytely®). Participants in the omnivore and EEN arms left the inpatient research unit only under the direct supervision of a research staff member. The vegan outpatients reported to the hospital twice on days 6,7 and 8 to receive antibiotics and to consume PEG on day 7. The first stool sample of each day of the inpatient groups was collected, aliquoted and frozen immediately at -80oC. Blood was collected on days 1, 5, 9, 12 and 15 from which plasma aliquots were immediately isolated and frozen at -80oC. The outpatient participants following the vegan diet also had blood collected on days 1, 5, 9, 12, and 15 from which plasma aliquots were immediately isolated and frozen at -80oC. Among these participants, the first stool of the day was collected at home daily and kept on ice packs until it was brought to the research unit where it could be aliquoted and frozen. Samples from vegans were received for aliquoting within 24 hours and on average within 4 hours (Wu et al., 2010). Day 0 stool was not collected from vegans since their diet did not change. The aliquoted amounts for all samples ranged from 500 mg to 1 g. The aliquots were taken from different areas of the sample. Remaining sample was then collected into one residual 50 ml conical tube with a tongue depressor. Any remaining stool was discarded. The University of Pennsylvania Institutional Review Board (IRB) approved the research protocol.
INSTITUTE
Broad Institute of MIT and Harvard
LAST_NAME
Clish
FIRST_NAME
Clary
ADDRESS
415 Main Street, Cambridge, MA, 02142, USA
EMAIL
clary@broadinstitute.org
PHONE
617-714-7654
NUM_GROUPS
3
TOTAL_SUBJECTS
30
NUM_MALES
20
NUM_FEMALES
10
STUDY_COMMENTS
plasma samples collected at baseline and 3-4 timepoints
The effect of fasting and sirtuin overexpression on serum metabolome.
STUDY_TYPE
untargeted metabolomics
STUDY_SUMMARY
The levels of the sirtuins SIRT1 and SIRT6 are regulated by nutrient availability in several mammalian tissues. In addition, overexpressing SIRT1 in mice improves healthspan, while SIRT6 overexpression increases both healthspan and lifespan. However, little is known about the impact of these sirtuins at the in vivo metabolomics level. Thus, we performed metabolomics on serum taken from 15 months old male mice overexpressing SIRT1, SIRT6 and SIRT1+SIRT6 as well as WT controls. Sera were obtained from mice at three nutritional time points - at fed state, after 4h morning fast and after 16h fast.
INSTITUTE
Bar Ilan University
DEPARTMENT
The Mina & Everard Goodman Faculty of Life Sciences
β-Adrenergic regulation of metabolism in macrophages
STUDY_SUMMARY
Macrophages have important roles in the immune system including clearing pathogens and wound healing. Metabolic phenotypes have been associated with functional phenotypes, where pro-inflammatory macrophages have an increased rate of glycolysis and anti-inflammatory macrophages primarily use oxidative phosphorylation. β-adrenoceptor (βAR) signalling in macrophages has been implicated in disease states such as cancer, atherosclerosis and rheumatoid arthritis. The impact of β-adrenoceptor signalling on macrophage metabolism has not been defined. Here we expand on defining the phenotype of macrophages treated with isoprenaline and describe the impact that βAR signalling has on the metabolome and proteome. We found that βAR signalling alters proteins involved in cytoskeletal rearrangement and redox control of the cell. We showed that βAR signalling in macrophages shifts glucose metabolism from glycolysis towards the tricarboxylic acid cycle and pentose phosphate pathways. We also show that βAR signalling perturbs purine metabolism by accumulating adenylate pools. Taken together these results indicate that βAR signalling shifts metabolism to support redox perturbations and upregulate proteins involved in cytoskeletal changes that may impact migration and phagocytosis processes.
INSTITUTE
Monash University
LAST_NAME
Peterson
FIRST_NAME
Amanda
ADDRESS
Drug delivery, disposition and dynamics, Pharmacy and Pharmaceutical Sciences, 381 Royal Parade, Parkville, Victoria, 3052, Australia
β-Adrenergic regulation of metabolism in macrophages (part-II)
STUDY_SUMMARY
Macrophages have important roles in the immune system including clearing pathogens and wound healing. Metabolic phenotypes have been associated with functional phenotypes, where pro-inflammatory macrophages have an increased rate of glycolysis and anti-inflammatory macrophages primarily use oxidative phosphorylation. β-adrenoceptor (βAR) signalling in macrophages has been implicated in disease states such as cancer, atherosclerosis and rheumatoid arthritis. The impact of β-adrenoceptor signalling on macrophage metabolism has not been defined. Here we expand on defining the phenotype of macrophages treated with isoprenaline and describe the impact that βAR signalling has on the metabolome and proteome. We found that βAR signalling alters proteins involved in cytoskeletal rearrangement and redox control of the cell. We showed that βAR signalling in macrophages shifts glucose metabolism from glycolysis towards the tricarboxylic acid cycle and pentose phosphate pathways. We also show that βAR signalling perturbs purine metabolism by accumulating adenylate pools. Taken together these results indicate that βAR signalling shifts metabolism to support redox perturbations and upregulate proteins involved in cytoskeletal changes that may impact migration and phagocytosis processes.
INSTITUTE
Monash University
LAST_NAME
Peterson
FIRST_NAME
Amanda
ADDRESS
Drug delivery, disposition and dynamics, Pharmacy and Pharmaceutical Sciences, 381 Royal Parade, Parkville, Victoria, 3052, Australia
β-Adrenergic regulation of metabolism in macrophages (part-III)
STUDY_SUMMARY
Macrophages have important roles in the immune system including clearing pathogens and wound healing. Metabolic phenotypes have been associated with functional phenotypes, where pro-inflammatory macrophages have an increased rate of glycolysis and anti-inflammatory macrophages primarily use oxidative phosphorylation. β-adrenoceptor (βAR) signalling in macrophages has been implicated in disease states such as cancer, atherosclerosis and rheumatoid arthritis. The impact of β-adrenoceptor signalling on macrophage metabolism has not been defined. Here we expand on defining the phenotype of macrophages treated with isoprenaline and describe the impact that βAR signalling has on the metabolome and proteome. We found that βAR signalling alters proteins involved in cytoskeletal rearrangement and redox control of the cell. We showed that βAR signalling in macrophages shifts glucose metabolism from glycolysis towards the tricarboxylic acid cycle and pentose phosphate pathways. We also show that βAR signalling perturbs purine metabolism by accumulating adenylate pools. Taken together these results indicate that βAR signalling shifts metabolism to support redox perturbations and upregulate proteins involved in cytoskeletal changes that may impact migration and phagocytosis processes.
INSTITUTE
Monash University
LAST_NAME
Peterson
FIRST_NAME
Amanda
ADDRESS
Drug delivery, disposition and dynamics, Pharmacy and Pharmaceutical Sciences, 381 Royal Parade, Parkville, Victoria, 3052, Australia
Genetic background shapes phenotypic response to diet for adiposity in the Collaborative Cross
STUDY_TYPE
Diet challenge
STUDY_SUMMARY
Defined as chronic excessive accumulation of adiposity, obesity results from long-term imbalance between energy intake and expenditure. The mechanisms behind how caloric imbalance occurs are complex and influenced by numerous biological and environmental factors, especially genetics and diet. Population-based diet recommendations have had limited success partly due to the wide variation in physiological responses across individuals when they consume the same diet. Thus, it is necessary to broaden our understanding of how individual genetics and diet interact relative to the development of obesity for improving weight loss treatment. To determine how consumption of diets with different macronutrient composition alter adiposity and other obesity-related traits in a genetically diverse population, we analyzed body composition, metabolic rate, clinical blood chemistries, and circulating metabolites in 22 strains of mice from the Collaborative Cross (CC), a highly diverse recombinant inbred mouse population, before and after 8 weeks of feeding either a high protein or high fat high sucrose diet. At both baseline and post-diet, adiposity and other obesity-related traits exhibited a broad range of phenotypic variation based on CC strain; diet-induced changes in adiposity and other traits also depended largely on CC strain. In addition to estimating heritability at baseline, we also quantified the effect size of diet for each trait, which varied by trait and experimental diet. Our findings identified CC strains prone to developing obesity, demonstrate the genotypic and phenotypic diversity of the CC for studying complex traits, and highlight the importance of accounting for genetic differences when making dietary recommendations.
Comparative metabolomics analysis of two Saccharomyces cerevisiae strains: the wild type and mtl1Δ, which carries a deletion of the mechanosensor Mtl1p.
STUDY_SUMMARY
To gather more in-depth knowledge of the Mtl1p mechanosensor's role in Saccharomyces cerevisiae metabolism, we conducted a comparative metabolomic analysis of two Saccharomyces cerevisiae strains: the wild type and mtl1Δ, which carries a deletion of the mechanosensor Mtl1p. Both strains were grown under normal conditions at 27°C. The most significant metabolic changes between these strains were related to amino acid metabolism, purine metabolism, and carboxylic acid metabolism.
INSTITUTE
University of Puerto Rico, Medical Sciences Campus
LAST_NAME
Chorna
FIRST_NAME
Nataliya
ADDRESS
University of Puerto Rico, Medical Sciences Campus, Department of Biochemistry, Main Building, 6th Floor, Room A-632, San Juan, PR 00935
Comparative metabolomics analysis of two Saccharomyces cerevisiae strains: the wild type and mtl1Δ, which carries a deletion of the mechanosensor Mtl1p (part-II)
STUDY_SUMMARY
To gather more in-depth knowledge of the Mtl1p mechanosensor's role in Saccharomyces cerevisiae metabolism, we conducted a comparative metabolomic analysis of two Saccharomyces cerevisiae strains: the wild type and mtl1Δ, which carries a deletion of the mechanosensor Mtl1p. Both strains were grown under normal conditions at 27°C. The most significant metabolic changes between these strains were related to amino acid metabolism, purine metabolism, and carboxylic acid metabolism.
INSTITUTE
University of Puerto Rico, Medical Sciences Campus
DEPARTMENT
Biochemistry
LAST_NAME
Chorna
FIRST_NAME
Nataliya
ADDRESS
University of Puerto Rico, Medical Sciences Campus, Department of Biochemistry, Main Building, 6th Floor, Room A-632, San Juan, PR 00935
Unique metabolomic profile of skeletal muscle in chronic limb threatening ischemia (organic phase samples)
STUDY_TYPE
NMR
STUDY_SUMMARY
This project is focused on a cross-sectional analysis of non-PAD controls and CLTI patients undergoing either a vascular intervention or undergoing limb amputation was performed and involved a detailed assessment of the limb muscle metabolome using HR-MAS and solution state NMR spectroscopy. It was hypothesized that patients undergoing limb amputation would present with altered muscle metaolite features compared with non-PAD controls.
INSTITUTE
University of Florida
DEPARTMENT
Applied Physiology and Kinesiology
LABORATORY
Rm 42 and Rm 43
LAST_NAME
Ryan
FIRST_NAME
Terence
ADDRESS
University of Florida, Applied Physiology and Kinesiology, 1864 stadium RD, Gainesville, FL 32611
EMAIL
ryant@ufl.edu
PHONE
352-294-1700
NUM_GROUPS
3
TOTAL_SUBJECTS
30
NUM_MALES
25
NUM_FEMALES
5
STUDY_COMMENTS
PAD metabolomic study via NMR. A detailed assessment of the limb muscle metabolome using semi-solid and solution state NMR spectroscopy
Unique metabolomic profile of skeletal muscle in chronic limb threatening ischemia (aqueous phase samples )
STUDY_TYPE
NMR
STUDY_SUMMARY
This project is focused on a cross-sectional analysis of non-PAD controls and CLTI patients undergoing either a vascular intervention or undergoing limb amputation was performed and involved a detailed assessment of the limb muscle metabolome using HR-MAS and solution state NMR spectroscopy. It was hypothesized that patients undergoing limb amputation would present with altered muscle metaolite features compared with non-PAD controls.
INSTITUTE
University of Florida
DEPARTMENT
Applied Physiology and Kinesiology
LABORATORY
Rm 42 and Rm 43
LAST_NAME
Ryan
FIRST_NAME
Terence
ADDRESS
University of Florida, Applied Physiology and Kinesiology, 1864 stadium RD, Gainesville, FL 32611
EMAIL
ryant@ufl.edu
PHONE
352-294-1700
NUM_GROUPS
3
TOTAL_SUBJECTS
30
NUM_MALES
25
NUM_FEMALES
5
STUDY_COMMENTS
PAD metabolomic study via NMR. A detailed assessment of the limb muscle metabolome using semi-solid and solution state NMR spectroscopy
Dietary composition analysis of chow diet and purified diet using untargeted metabonomics
STUDY_SUMMARY
Dietary patterns and psychosocial factors, ubiquitous part of modern lifestyle, critically shape the gut microbiota and human health. However, it remains obscure how dietary and psychosocial inputs coordinately modulate the gut microbiota and host impact. Here, we show that dietary raffinose metabolism to fructose couples stress-induced gut microbial remodeling to intestinal stem cells (ISC) renewal and epithelial homeostasis. Chow diet (CD) and purified diet (PD) confer distinct vulnerability to gut epithelial injury, microbial alternation and ISC dysfunction in chronically restrained mice. CD preferably enriches Lactobacillus reuteri, and its colonization is sufficient to rescue stress-triggered epithelial injury.
Targeted metabolomics analysis with raffinose-rich diet in mouse ileum
STUDY_TYPE
Analysis of fructose level in ileum of stressed mouse fed with raffinose-rich diet
STUDY_SUMMARY
Purified diet (AIN-93G) supplemented with raffinose was prepared. The mice were maintained on the separate diet for at least 1 week before the initiation of experiment.Chronic restraint stress (RS) in mice was performed 14 days.After sacrifice, the ileum of mice were used to analysis.
Tissue-specific 1H-NMR metabolomic profiling in mice with adenine-induced chronic kidney disease - aqueous phase Kidney (part-I)
STUDY_TYPE
Metabolomic profiling of the heart, liver, kidney, and skeletal muscles obtained from mice with and without CKD via 1H NMR
STUDY_SUMMARY
This project is focused on a metabolomic analyses of the heart, liver, kidney, and skeletal muscles obtained from mice with and without CKD. To accomplish this objective, we extracted tissues from mice with CKD induced by long-term (24 week) adenine-supplemented diet as well as their control-diet fed counterparts with normal kidney function. Metabolites were extracted from tissues and 1H nuclear magnetic resonance (NMR) was performed and coupled with multivariate statistical analysis.
INSTITUTE
University of Florida
DEPARTMENT
Applied Physiology and Kinesiology
LABORATORY
Rm 42 and Rm 43
LAST_NAME
Ryan
FIRST_NAME
Terence
ADDRESS
1864 Stadium Rd, FLG 114, Gainesville, FL, 32611, USA
Tissue-specific 1H-NMR metabolomic profiling in mice with adenine-induced chronic kidney disease - organic phase Kidney (part-II)
STUDY_TYPE
Metabolomic profiling of the heart, liver, kidney, and skeletal muscles obtained from mice with and without CKD via 1H NMR
STUDY_SUMMARY
This project is focused on a metabolomic analyses of the heart, liver, kidney, and skeletal muscles obtained from mice with and without CKD. To accomplish this objective, we extracted tissues from mice with CKD induced by long-term (24 week) adenine-supplemented diet as well as their control-diet fed counterparts with normal kidney function. Metabolites were extracted from tissues and 1H nuclear magnetic resonance (NMR) was performed and coupled with multivariate statistical analysis.
INSTITUTE
University of Florida
DEPARTMENT
Applied Physiology and Kinesiology
LABORATORY
Rm 42 and Rm 43
LAST_NAME
Ryan
FIRST_NAME
Terence
ADDRESS
1864 Stadium Rd, FLG 114, Gainesville, FL, 32611, USA
Tissue-specific 1H-NMR metabolomic profiling in mice with adenine-induced chronic kidney disease - aqueous phase Heart (part-III)
STUDY_TYPE
Metabolomic profiling of the heart, liver, kidney, and skeletal muscles obtained from mice with and without CKD via 1H NMR
STUDY_SUMMARY
This project is focused on a metabolomic analyses of the heart, liver, kidney, and skeletal muscles obtained from mice with and without CKD. To accomplish this objective, we extracted tissues from mice with CKD induced by long-term (24 week) adenine-supplemented diet as well as their control-diet fed counterparts with normal kidney function. Metabolites were extracted from tissues and 1H nuclear magnetic resonance (NMR) was performed and coupled with multivariate statistical analysis.
INSTITUTE
University of Florida
DEPARTMENT
Applied Physiology and Kinesiology
LABORATORY
Rm 42 and Rm 43
LAST_NAME
Ryan
FIRST_NAME
Terence
ADDRESS
1864 Stadium Rd, FLG 114, Gainesville, FL, 32611, USA
Tissue-specific 1H-NMR metabolomic profiling in mice with adenine-induced chronic kidney disease - organic phase Heart (part-IV)
STUDY_TYPE
Metabolomic profiling of the heart, liver, kidney, and skeletal muscles obtained from mice with and without CKD via 1H NMR
STUDY_SUMMARY
This project is focused on a metabolomic analyses of the heart, liver, kidney, and skeletal muscles obtained from mice with and without CKD. To accomplish this objective, we extracted tissues from mice with CKD induced by long-term (24 week) adenine-supplemented diet as well as their control-diet fed counterparts with normal kidney function. Metabolites were extracted from tissues and 1H nuclear magnetic resonance (NMR) was performed and coupled with multivariate statistical analysis.
INSTITUTE
University of Florida
DEPARTMENT
Applied Physiology and Kinesiology
LABORATORY
Rm 42 and Rm 43
LAST_NAME
Ryan
FIRST_NAME
Terence
ADDRESS
1864 Stadium Rd, FLG 114, Gainesville, FL, 32611, USA
Tissue-specific 1H-NMR metabolomic profiling in mice with adenine-induced chronic kidney disease - aqueous phase Liver (part-V)
STUDY_TYPE
Metabolomic profiling of the heart, liver, kidney, and skeletal muscles obtained from mice with and without CKD via 1H NMR
STUDY_SUMMARY
This project is focused on a metabolomic analyses of the heart, liver, kidney, and skeletal muscles obtained from mice with and without CKD. To accomplish this objective, we extracted tissues from mice with CKD induced by long-term (24 week) adenine-supplemented diet as well as their control-diet fed counterparts with normal kidney function. Metabolites were extracted from tissues and 1H nuclear magnetic resonance (NMR) was performed and coupled with multivariate statistical analysis.
INSTITUTE
University of Florida
DEPARTMENT
Applied Physiology and Kinesiology
LABORATORY
Rm 42 and Rm 43
LAST_NAME
Ryan
FIRST_NAME
Terence
ADDRESS
1864 Stadium Rd, FLG 114, Gainesville, FL, 32611, USA
Tissue-specific 1H-NMR metabolomic profiling in mice with adenine-induced chronic kidney disease - organic phase Liver (part-VI)
STUDY_TYPE
Metabolomic profiling of the heart, liver, kidney, and skeletal muscles obtained from mice with and without CKD via 1H NMR
STUDY_SUMMARY
This project is focused on a metabolomic analyses of the heart, liver, kidney, and skeletal muscles obtained from mice with and without CKD. To accomplish this objective, we extracted tissues from mice with CKD induced by long-term (24 week) adenine-supplemented diet as well as their control-diet fed counterparts with normal kidney function. Metabolites were extracted from tissues and 1H nuclear magnetic resonance (NMR) was performed and coupled with multivariate statistical analysis.
INSTITUTE
University of Florida
DEPARTMENT
Applied Physiology and Kinesiology
LABORATORY
Rm 42 and Rm 43
LAST_NAME
Ryan
FIRST_NAME
Terence
ADDRESS
1864 Stadium Rd, FLG 114, Gainesville, FL, 32611, USA
Tissue-specific 1H-NMR metabolomic profiling in mice with adenine-induced chronic kidney disease - aqueous phase Quadricep (part-VII)
STUDY_TYPE
Metabolomic profiling of the heart, liver, kidney, and skeletal muscles obtained from mice with and without CKD via 1H NMR
STUDY_SUMMARY
This project is focused on a metabolomic analyses of the heart, liver, kidney, and skeletal muscles obtained from mice with and without CKD. To accomplish this objective, we extracted tissues from mice with CKD induced by long-term (24 week) adenine-supplemented diet as well as their control-diet fed counterparts with normal kidney function. Metabolites were extracted from tissues and 1H nuclear magnetic resonance (NMR) was performed and coupled with multivariate statistical analysis.
INSTITUTE
University of Florida
DEPARTMENT
Applied Physiology and Kinesiology
LABORATORY
Rm 42 and Rm 43
LAST_NAME
Ryan
FIRST_NAME
Terence
ADDRESS
1864 Stadium Rd, FLG 114, Gainesville, FL, 32611, USA
Tissue-specific 1H-NMR metabolomic profiling in mice with adenine-induced chronic kidney disease - organic phase Quadricep (part-VIII)
STUDY_TYPE
Metabolomic profiling of the heart, liver, kidney, and skeletal muscles obtained from mice with and without CKD via 1H NMR
STUDY_SUMMARY
This project is focused on a metabolomic analyses of the heart, liver, kidney, and skeletal muscles obtained from mice with and without CKD. To accomplish this objective, we extracted tissues from mice with CKD induced by long-term (24 week) adenine-supplemented diet as well as their control-diet fed counterparts with normal kidney function. Metabolites were extracted from tissues and 1H nuclear magnetic resonance (NMR) was performed and coupled with multivariate statistical analysis.
INSTITUTE
University of Florida
DEPARTMENT
Applied Physiology and Kinesiology
LABORATORY
Rm 42 and Rm 43
LAST_NAME
Ryan
FIRST_NAME
Terence
ADDRESS
1864 Stadium Rd, FLG 114, Gainesville, FL, 32611, USA
Metabolomics analysis of Vehicle (DMSO/PBS; (1:1) v/v) and DRB18 (10 mg/kg) treated A549 xenograft tumors
STUDY_TYPE
Anticancer compound treatment experiment in vivo
STUDY_SUMMARY
A549 xenograft tumors were treated with (DMSO/PBS; (1:1) v/v) and DRB18 (10 mg/kg) for 5 weeks. The mice were then sacrificed and tumors were then excised. Tumors were then subjected to untargeted metabolomics analysis.
INSTITUTE
Ohio University
DEPARTMENT
Biological Sciences
LABORATORY
Dr. Xiaozhuo Chen, Edison biotechnology Institute
LAST_NAME
Shriwas
FIRST_NAME
Pratik
ADDRESS
172 Water Tower, Building 25, The Ridges, Konnekar Research Centerm Athens Ohio - 45701, USA
EMAIL
ps774614@ohio.edu
PHONE
7406033801
NUM_GROUPS
2
TOTAL_SUBJECTS
20
NUM_MALES
20
ANALYSIS_TYPE_DETAIL
Untargeted Metabolomics analysis of A549 xenograft tumors
Plasma Metabolomic signatures of COPD in a SPIROMICS cohort
STUDY_SUMMARY
The Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) (ClinicalTrials.gov Identifier: NCT01969344) includes 2,771 subjects, aged 40-80 years with at least 20 pack-years of smoking. An additional 202 subjects were never smokers. Fasting blood drawn at the enrollment visit using a p100 tube. The first 649 subjects who returned for a 5-7 year visit (Visit 5) were selected for this study. The blood profiled were from the year 1 visit.
In Vitro Characterization and Metabolomic Analysis of Cold-Stored Platelets
STUDY_SUMMARY
Platelet concentrates are currently stored at room temperature (RPs) under constant agitation for up to 5-7 days depending on national regulations. However, platelet quality deteriorates during storage and room temperature storage also increases the risk of bacterial growth. Previous studies have shown that cold-stored platelets (CPs) have higher hemostatic function and can be stored for up to three weeks. While these studies have compared the metabolic phenotypes of CPs and RPs, they have not compared the impact of storage temperature and cold agitation (CPAs) on platelet function, nor have they identified metabolic correlates to such parameters. In vitro analysis showed CPAs and CPs had reduced count, faster CD62P expression and increased lactadherin binding. Furthermore, CPAs and CPs had higher maximal aggregation and a reduced aggregation lag phase compared to RPs. Metabolomic analysis revealed CPAs and CPs exhibited lower oxidative stress shown by preserved glutathione and pentose phosphate pools. CPAs and CPs also had reduced markers of beta-oxidation and amino acid catabolism demonstrating reduced needs for energy. Agitation did not significantly impact in vitro function or metabolomic parameters of cold-stored platelets. Correlation of in vitro and metabolomic results highlighted important metabolites that may contribute to stored platelet functions.
Variability in metabolomic profiles among unique genotypes of Acropora cervicornis (part -II)
STUDY_TYPE
intraspecific variability
STUDY_SUMMARY
This project aims to identify differences in metabolomic profiles among seven known, unique genotypes of the threatened staghorn coral Acropora cervicornis.
INSTITUTE
University of Florida
DEPARTMENT
SECIM
LAST_NAME
Patterson
FIRST_NAME
Joshua
ADDRESS
Florida Aquarium Center for Conservation, 529 Estuary Shore Lane, Apollo Beach, FL 33572
Atypical Molecular Basis for Drug Resistance to Mitochondrial AQ: A Function Inhibitors in Plasmodium falciparum
STUDY_SUMMARY
In this study, we present a clear genotype for the P. falciparum SB1-A6 acridone-resistant clonal parasite strain and, through a combination of targeted and whole-cell methods, establish that the mechanism of resistance to both cytochrome bc1 and DHODH inhibitors results from the contribution of multiple genetic polymorphisms. We find that P. falciparum SB1-A6 accumulates both a copy number variation and a specific mutation in PfDHODH, and both of these genetic polymorphisms contribute to the panresistant phenotype. This study uncovers a mechanism of cross-resistance between PfDHODH and mtETC inhibitors and serves as a cautionary note to future antimalarial combination therapy formulations containing such drugs.
INSTITUTE
U.S. Food & Drug Administration
LAST_NAME
Painter
FIRST_NAME
Heather
ADDRESS
10903 New Hampshire Ave., WO 52/72-5324, Silver Spring, MD 20993
Characterization of anaphylaxis reveals different metabolic changes depending on severity and triggers.
STUDY_SUMMARY
Background: Despite its increasing incidence, the underlying molecular processes of anaphylaxis remain unclear and there are not known biomarkers for appropriate diagnosis. The mechanism associated to the reactions still needs to be clarified in humans. The rapid onset and potentially fatal outcome in the absence of managed treatment, prevent its study and prompt obvious technical and ethical implications. Methods: Twenty episodes of anaphylaxis were analyzed. Sera was collected at different times: during the acute phase (T1), the recovery phase (T2) and around 2-3 months after the anaphylactic reaction (T0). The analysis included untargeted metabolomics combining liquid chromatography coupled to mass spectrometry (LC-MS) and proton-nuclear magnetic resonance (1H-NMR). Reactions were classified according to the trigger (food and/or drug) and severity (moderate and severe). Results: “Food T1 vs T2” and “moderate T1 vs T2” anaphylaxis comparisons showed clear metabolic patterns during the onset of an anaphylactic reaction, which differed from those induced by drugs, food+drug or severe anaphylaxis “T1 vs T2”. Moreover, the model of food anaphylaxis was able to distinguish the well-characterized IgE (beta-lactam) from non-IgE- mediated anaphylaxis (NSAIDs), suggesting a differential metabolic pathway associated with the mechanism of action. Moreover, metabolic differences between “moderate vs severe” at T1 and T0 were studied. Among the metabolites, glucose, lipids, cortisol, betaine and oleamide were observed altered. Conclusions: The results of the study provide the first evidence that different anaphylactic triggers, induce differential metabolic changes. Besides, the basal status might identify high risk patients, thus opening new ways to understand, diagnose and treat anaphylaxis.
Extension of Diagnostic Fragmentation Filtering for Automated Discovery in DNA Adductomics
STUDY_SUMMARY
Development of high resolution/accurate mass liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS) methodology enables the characterization of covalently modified DNA induced by interaction with genotoxic agents in complex biological samples. Constant neutral loss monitoring of 2´-deoxyribose or the nucleobases using data-dependent acquisition represents a powerful approach for the unbiased detection of DNA modifications (adducts). The lack of available bioinformatics tools necessitates manual processing of acquired spectral data and hampers high throughput application of these techniques. To address this limitation, we present an automated workflow for the detection and curation of putative DNA adducts by using diagnostic fragmentation filtering of LC-MS/MS experiments within the open-source software MZmine. The workflow utilizes a new feature detection algorithm, DFBuilder, which employs diagnostic fragmentation filtering using a user-defined list of fragmentation patterns to reproducibly generate feature lists for precursor ions of interest. The DFBuilder feature detection approach readily fits into a complete small molecule discovery workflow and drastically reduces the processing time associated with analyzing DNA adductomics results. We validate our workflow using a mixture of authentic DNA adduct standards and demonstrate the effectiveness of our approach by reproducing and expanding the results of a previously published study of colibactin-induced DNA adducts. The reported workflow serves as a technique to assess the diagnostic potential of novel fragmentation pattern combinations for the unbiased detection of chemical classes of interest.
INSTITUTE
University of Minnesota
DEPARTMENT
School of Public Health, Division of Environmental Health Sciences
LABORATORY
Balbo Research Group
LAST_NAME
Murray
FIRST_NAME
Kevin
ADDRESS
2-210 CCRB, 2231 6th St SE, Minneapolis, MN 55455
EMAIL
murra668@umn.edu
PHONE
612-626-2182
NUM_GROUPS
1
TOTAL_SUBJECTS
3
STUDY_COMMENTS
Synthetic samples of authentic standards for workflow testing and validation.
PUBLICATIONS
Murray K.J.; Carlson E.S.; Stornetta A.; Balskus E.P.; Villalta P.W.; Balbo S. Extension of Diagnostic Fragmentation Filtering for Automated Discovery in DNA Adductomics. Anal. Chem. 2021. (In Revision).
Four different treatment groups were used for metabolite characterization: 5 dpf larvae with/without beta-cell ablation and with/without folinic acid treatment.
A gut microbe-focused metabolomics pipeline enables mechanistic interrogation of microbiome metabolism
STUDY_SUMMARY
Gut microbes modulate host phenotypes and are associated with numerous health effects in humans, ranging from cancer immunotherapy response to metabolic disease and obesity. However, difficulty in accurate and high-throughput functional analysis of human gut microbes has hindered defining mechanistic connections between individual microbial strains and host phenotypes. One key way the gut microbiome influences host physiology is through the production of small molecules1–3, yet progress in elucidating this chemical interplay has been hindered by limited tools calibrated to detect products of anaerobic biochemistry in the gut. Here we construct a microbiome-focused, integrated mass-spectrometry pipeline to accelerate the identification of microbiota-dependent metabolites (MDMs) in diverse sample types. We report the metabolic profiles of 178 gut microbe strains using our library of 833 metabolites. Leveraging this metabolomics resource we establish deviations in the relationships between phylogeny and metabolism, use machine learning to discover novel metabolism in Bacteroides, and employ comparative genomics-based discovery of candidate biochemical pathways. MDMs can be detected in diverse body fluids in gnotobiotic and conventional mice and traced back to corresponding metabolomic profiles of cultured bacteria. Collectively, our microbiome-focused metabolomics pipeline and interactive metabolomics profile explorer are a powerful tool for characterizing microbe and microbe-host interactions.
INSTITUTE
Stanford University
DEPARTMENT
Microbiology and Immunology
LABORATORY
Justin Sonnenburg
LAST_NAME
Van Treuren
FIRST_NAME
Will
ADDRESS
Sherman Fairchild Building, 299 Campus Drive, Stanford CA, 94305
A gut microbe-focused metabolomics pipeline enables mechanistic interrogation of microbiome metabolism.
STUDY_SUMMARY
Gut microbes modulate host phenotypes and are associated with numerous health effects in humans, ranging from cancer immunotherapy response to metabolic disease and obesity. However, difficulty in accurate and high-throughput functional analysis of human gut microbes has hindered defining mechanistic connections between individual microbial strains and host phenotypes. One key way the gut microbiome influences host physiology is through the production of small molecules hindered by limited tools calibrated to detect products of anaerobic biochemistry in the gut. Here we construct a microbiome-focused, integrated mass-spectrometry pipeline to accelerate the identification of microbiota-dependent metabolites (MDMs) in diverse sample types. We report the metabolic profiles of 178 gut microbe strains using our library of 833 metabolites. Leveraging this metabolomics resource we establish deviations in the relationships between phylogeny and metabolism, use machine learning to discover novel metabolism in Bacteroides, and employ comparative genomics-based discovery of candidate biochemical pathways. MDMs can be detected in diverse body fluids in gnotobiotic and conventional mice and traced back to corresponding metabolomic profiles of cultured bacteria. Collectively, our microbiome-focused metabolomics pipeline and interactive metabolomics profile explorer are a powerful tool for characterizing microbe and microbe-host interactions.
Untargeted metabolomic analysis of human blood samples via qualitative GC-MS for T1D biomarker identification
STUDY_TYPE
Qualitative GC-MS biomarker identification
STUDY_SUMMARY
"Blood from human subjects at high risk for T1D (and healthy controls; n=4 each) were subjected to parallel unlabeled proteomics, metabolomics, lipidomics, and transcriptomics. The integrated dataset was analyzed using Ingenuity Pathway Analysis (IPA) software for disturbances in the at-risk subjects compared to the controls. The final quadra-omics dataset contained 2292 proteins, 328 miRNAs, 75 metabolites, and 41 lipids that were detected in all samples. Disease/function enrichment analyses consistently indicated increased activation, proliferation, and migration of immune cells, particularly, CD4 T-lymphocytes and macrophages. Integrated molecular network predictions highlighted central involvement and activation of NF-κB, TGF-β, VEGF, arachidonic acid, and arginase, and inhibition of miRNA Let-7a-5p. Parallel multi-omics provided a comprehensive picture of disturbances in high-risk T1D subjects and helped identify an associated integrated biomarker signature, which could ultimately facilitate the classification of T1D progressors from non-progressors."
INSTITUTE
Duke University
DEPARTMENT
Duke Molecular Physiology Institute, School of Medicine
A cross-sectional study of functional and metabolic changes during aging through the lifespan in male mice (Liver) part-III
STUDY_SUMMARY
Aging is associated with distinct phenotypical, physiological, and functional changes, leading to the onset of disease and death. The progression of aging-related traits varies widely among individuals, influenced by their environment, lifestyle, and genetics. In this study, we performed physiologic and functional tests cross-sectionally throughout the entire lifespan of male C57BL/6N mice. In parallel, metabolomics analyses in serum, brain, liver, heart, and skeletal muscle were also performed to identify signatures associated with frailty and age-dependent functional decline. Our findings indicate that the decline in gait speed as a function of age and frailty is associated with dramatic increases in the energetic cost of physical activity and decreases in working capacity. Aging and functional decline prompt organs to rewire their substrate selection and metabolism towards redox-related pathways, mainly in liver and heart. Collectively, the data provide a framework to further understand and characterize processes of aging at the individual and organ levels.
INSTITUTE
National Institutes of Health
DEPARTMENT
NIA
LABORATORY
Experimental Gerontology Section and Translational Gerontology Branch
LAST_NAME
de Cabo
FIRST_NAME
Rafael
ADDRESS
251 Bayview Blvd. Suite 100/Room 5C214. Baltimore, MD 21224
Machine learning-enabled renal cell carcinoma status prediction using multi-platform urine-based metabolomics NMR (part-II)
STUDY_SUMMARY
Currently, Renal Cell Carcinoma (RCC) is identified through expensive cross-sectional imaging, frequently followed by renal mass biopsy, which is invasive and subject to sampling errors. Hence, there is a critical need for a non-invasive diagnostic assay. RCC is a disease of altered cellular metabolism with the tumor(s) in close proximity to the urine in the kidney suggesting metabolomic profiling would be an excellent choice for assay development. Here, we applied liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR), and machine learning (ML) for the discovery of candidate metabolic panels for RCC. The study cohort consists of 82 RCC patients and 174 healthy controls, these were separated into two sub-cohorts: model cohort and the test cohort. Discriminatory metabolic features were selected in the model cohort, using univariate, wrapper, and embedded methods of feature selection. Three ML techniques with different induction biases were used for training and hyperparameter tuning. Final assessment of RCC status prediction was made using the test cohort with the selected biomarkers and the tuned ML algorithms. A seven-metabolite panel consisting of endogenous and exogenous metabolites enabled the prediction of RCC with 88% accuracy, 94% sensitivity, and 85% specificity in the test cohort, with an AUC of 0.98.
Detecting sex-related changes to the metabolome of a critically endangered freshwater crayfish during the mating season
STUDY_TYPE
LC-MS analysis of crustacean haemolymph
STUDY_SUMMARY
Captive breeding is a vital tool in the conservation of highly endangered species, as it is for the Margaret River hairy marron, Cherax tenuimanus, from the south west of Australia. A close relative, Cherax cainii, has almost completely displaced C. tenuimanus in the wild and is a successful aquaculture species, whereas C. tenuimanus has performed poorly in captivity. We used untargeted liquid chromatography-mass spectrometry to obtain metabolomic profiles of female and male C. tenuimanus held in controlled aquarium conditions during their reproductive period. Using repeated haemolymph sampling we tracked the metabolomic profiles of animals just prior to and for a period of up to 34 days after pairing with a similar sized potential mate. We identified 54 reproducible annotated metabolites including amino acids, fatty acids, biogenic amines, purine and pyrimidine metabolites and excretion metabolites. Hierarchical clustering analysis distinguished five metabolite clusters. Principal component-canonical variate analysis clearly distinguished females from males, both unpaired and paired; similar trends in profile changes in both sexes after pairing; and a striking shift in males upon pairing. We discuss three main patterns of metabolomic responses: differentiation between sexes; reactive responses to the disturbance of pairing; and convergent response to the disturbance of pairing for males. Females generally had higher concentrations of metabolites involved in metabolic rate, mobilisation of energy stores and stress. Responses to the disturbance of pairing were also related to elevated stress. Females were mobilising lipid stores to deposit yolk, whereas males had a rapid and strong response to pairing, with shifts in metabolites associated with gonad development and communication, indicating males could complete reproductive readiness only once paired with a female. The metabolomic profiles support a previously proposed potential mechanism for displacement of C. tenuimanus by C. cainii in the wild and identify several biomarkers for testing hypotheses regarding reproductive success using targeted metabolomics.
INSTITUTE
Edith Cowan University
DEPARTMENT
School of Science
LAST_NAME
Lette
FIRST_NAME
Emily
ADDRESS
270 Joondalup Drive, Joondalup, WA, 6027, Australia
Lipidomics dataset of Danio rerio optic nerve regeneration model
STUDY_SUMMARY
The right optic nerve of 1 year old female and male Danio rerio were crushed and collected three days after. Matching controls of uninjured eyes were also collected. The tissue was dissected from euthanized fish and “flash” frozen on dry ice in Eppendorf tubes. Due to the small size of the nerves, for each category (female crush, female control, male crush, male control) n=24 the samples were pooled. The brain from one male fish was also collected for control/calibration. Lipid extraction was done with the Bligh and Dyer [2] method, followed by untargeted liquid chromatography-mass spectrometry (LC MS-MS) lipid profiling using a Q-Exactive Orbitrap instrument coupled with Vanquish Horizon Binary UHPLC LC-MS system. The lipids were identified and quantified with LipidSearch 4.2.21 and the statistical analysis was conducted through Metaboanalyst 5.0.
Understanding systemic and local inflammation induced by nasal polyposis: role of the allergic phenotype (part-II)
STUDY_SUMMARY
Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by persistent symptoms associated to the development of nasal polyps. To this day, the molecular mechanisms involved are still not well defined. However, it has been suggested that a sustained inflammation as allergy is involved in its onset. In this pilot study, we aimed to look into the effect of the allergic status of the patient and in their underlying mechanisms. To achieve this, we recruited 22 patients with CRSwNP and classified them in non-allergic and allergic using ImmunoCAP ISAC molecular diagnosis. Plasma samples were analyzed using liquid chromatography coupled to mass spectrometry (LC-MS). Subsequently, the identified changed metabolites from plasma that were commercially available were then analyzed by targeted analysis in some nasal polyps. Additionally, nasal polyp and mucosa tissue samples were examined for eosinophils and neutrophils. We found that 9 out of the 22 patients were sensitized to some aeroallergens (named as allergic). The other 13 patients had no sensitizations (non-allergic). Regarding metabolomics, we found that bilirubin, cortisol, lysophosphatidylcholines (LPCs) 16:0, 18:0 and 20:4 and lysophosphatidylinositol (LPI) 20:4, metabolites that are usually related to a sustained allergic inflammation, were unexpectedly increased in the plasma of non-allergic patients with CRSwNP compared to allergic patients with CRSwNP. LPC 16:0, LPC 18:0 and LPI 20:4 metabolites followed the same trend in the nasal polyp as they did in plasma. Comparison of nasal polyps with nasal mucosa tissue showed a significant increase in eosinophils (p < 0.001) and neutrophils (p < 0.01) in allergic patients with CRSwNP. There were also more eosinophils in the polyps of non-allergic patients with CRSwNP than in their nasal mucosa (p <0.01). The polyps from non-allergic patients with CRSwNP had less eosinophils than the polyps of allergic patients with CRSwNP (p < 0.05). Our data suggests that there is a systemic inflammatory response associated to CRSwNP in the absence of allergy, which could be accountable for the nasal polyp development. Allergic patients with CRSwNP presented a higher number of eosinophils located in nasal polyps suggesting that eosinophilia might be connected to the development of nasal polyps in these patients.
INSTITUTE
CEMBIO
LAST_NAME
Delgado Dolset
FIRST_NAME
María Isabel
ADDRESS
Urb. Montepríncipe s/n, Ctra. Boadilla del Monte km 5.3, Madrid, Madrid, 28668, Spain
1H HRMAS NMR Spectroscopy based Metabolomics of Urinary Bladder Tissues from NMIBC Patients
STUDY_TYPE
NMR Based Metabolomics
STUDY_SUMMARY
Application of 1H HRMAS NMR Spectroscopy to study malignancy induced metabolomic changes in urinary bladder tissues from 26 NMIBC patients. Predict the possible biomarker of NMIBC in urinary bladder tissues.
INSTITUTE
Centre of Biomedical Research, Lucknow, India
DEPARTMENT
Department of Radiology
LABORATORY
NMR Based Metabolomics
LAST_NAME
Roy
FIRST_NAME
Raja
ADDRESS
Centre of Biomedical Research, Lucknow, India 226014
Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis
STUDY_TYPE
Targeted metabolomics
STUDY_SUMMARY
GUT103 and GUT108, live biotherapeutic products rationally designed to complement missing or underrepresented functions in the dysbiotic microbiome of IBD patients; they address upstream targets, rather than targeting a single cytokine to block downstream inflammation responses. Systematic colonization experiments in colitis mouse models were performed to test their therapeutic effects. Targeted fecal metabolomics data uploaded here of bile acids, short-chain fatty acids, and tryptophan metabolites provides a unique metabolome perspective for evaluation of the therapeutic potential of GUT103 and GUT108.
INSTITUTE
University of North Carolina at Chapel Hill
LABORATORY
Gusto Global LLC.
LAST_NAME
Lai
FIRST_NAME
Yunjia
ADDRESS
1104 MHRC, 135 Dauer Drive, Chapel Hill, NC 27599, USA
Dual RNA regulator VcdRP in V. cholerae modulates central metabolism
STUDY_SUMMARY
Bacterial small RNAs (sRNAs) are well-known to modulate gene expression by base-pairing with trans-coded transcripts and are typically considered to be non-coding. However, several sRNAs have been reported to also contain an open reading frame and thus are considered dual-function regulators. We discovered a dual-function regulator from Vibrio cholerae, called VcdRP, harboring a 29 amino acid protein (VcdP), as well as a base-pairing sequence. In this study, we measured the metabolite abundance of glycolytic and citric acid cycle intermediates using LC-MS.
A reductionist approach using primary and metastatic cell-derived extracellular vesicles reveals hub proteins associated with oral cancer prognosis
STUDY_SUMMARY
Oral squamous cell carcinoma (OSCC) has high mortality rates that are largely associated with lymph node metastasis. However, the molecular mechanisms that drive OSCC metastasis are unknown. Extracellular vesicles (EVs) are membrane-bound particles that play a role in intercellular communication and impact cancer development and progression. Thus, profiling EVs would be of great significance to decipher the role of EV cargo in OSCC metastasis. For that purpose, we used a reductionist approach to map the proteomic, miRNA, metabolomic, and lipidomic profiles of extracellular vesicles (EVs) derived from human primary tumor (SCC-9) cells and matched lymph node metastases (LN1) cells. Distinct omics profiles were associated with the metastatic phenotype, including 670 proteins, 217 miRNAs, 26 metabolites, and 64 lipids differentially abundant between LN1- and SCC-9-derived EVs. A multi-omics integration identified 11 ‘hub proteins’ significantly decreased at the metastatic site compared to primary tumor-derived EVs. We confirmed the validity of these findings with analysis of data from multiple public databases, and found that low abundance of seven hub proteins in metastatic EVs is correlated with reduced survival and tumor aggressiveness in cancer patients. In summary, this multi-omics approach identified proteins transported by EVs that are associated with metastasis, and which may potentially serve as prognostic markers in OSCC.
INSTITUTE
National Center for Research in Energy and Materials
Application of the redox metabolite detection method for mouse liver
STUDY_SUMMARY
This study was aimed at optimizing redox metabolites detection from mammalian tissues. Three different chromatographic conditions were compared as well as three different extraction conditions. This study was run on ZIC-pHILIC chromatography. This study is an independent replicate.
INSTITUTE
Boston Children's Hospital, Harvard Medical School
Application of the redox metabolite detection method for mouse kidney
STUDY_SUMMARY
This study was aimed at optimizing redox metabolites detection from mammalian tissues. Three different chromatographic conditions were compared as well as three different extraction conditions. This study was run on ZIC-pHILIC chromatography. This study is an independent replicate
INSTITUTE
Boston Children's Hospital, Harvard Medical School
Application of the redox metabolite detection method for mouse biofluids
STUDY_SUMMARY
This study was aimed at optimizing redox metabolites detection from mammalian biofluids. Three different extraction conditions were compared, including derivatization of glutathione. This study was with mouse cerebrospinal fluid.
INSTITUTE
Boston Children's Hospital, Harvard Medical School
Application of the redox metabolite detection method for mouse kidney (part II)
STUDY_SUMMARY
This study was aimed at optimizing redox metabolites detection from mammalian tissues. Three different chromatographic conditions were compared as well as three different extraction conditions. This study was run on ZIC-pHILIC chromatography. This study is an independent repeat.
INSTITUTE
Boston Children's Hospital, Harvard Medical School
Application of the redox metabolite detection method for mouse liver (part II)
STUDY_SUMMARY
This study was aimed at optimizing redox metabolites detection from mammalian tissues. Three different chromatographic conditions were compared as well as three different extraction conditions. This study was run on ZIC-pHILIC chromatography. This study is an independent repeat.
INSTITUTE
Boston Children's Hospital, Harvard Medical School
Application of the redox metabolite detection method for profiling redox state following pharmacologic perturbation with methotrexate
STUDY_SUMMARY
This study aimed to test methods for detection of redox metabolites from mammalian cells upon metabolism perturbation by methotrexate. Three time points and three extraction conditions are explored
INSTITUTE
Boston Children's Hospital, Harvard Medical School
Optimization of redox metabolite detection in mammalian cells (part I)
STUDY_SUMMARY
Conditions were tested to optimize number of cells and extraction buffer for the detection of redox reactive metabolites from mammalian cells. Four different extraction buffers were compared. Derivatization of glutathione was explored as a condition as well. This is an independent repeat.
INSTITUTE
Boston Children's Hospital, Harvard Medical School
Application of the redox metabolite detection method for mammalian tissues (part I)
STUDY_SUMMARY
This study was aimed at optimizing redox metabolites detection from mammalian tissues. Three different chromatographic conditions were compared as well as three different extraction conditions. This study was run on LUNA NH2 HILIC chromatography
INSTITUTE
Boston Children's Hospital, Harvard Medical School
Application of the redox metabolite detection method for mammalian tissues (part II)
STUDY_SUMMARY
This study was aimed at optimizing redox metabolites detection from mammalian tissues. Three different chromatographic conditions were compared as well as three different extraction conditions. This study was run on Accucore Amide HILIC chromatography
INSTITUTE
Boston Children's Hospital, Harvard Medical School
Application of the redox metabolite detection method for mammalian tissues (part III)
STUDY_SUMMARY
This study was aimed at optimizing redox metabolites detection from mammalian tissues. Three different chromatographic conditions were compared as well as three different extraction conditions. This study was run on ZIC-pHILIC chromatography.
INSTITUTE
Boston Children's Hospital, Harvard Medical School
Application of the redox metabolite detection method for profiling redox state following pharmacologic perturbations of redox balance in cells (part I)
STUDY_SUMMARY
This study aimed to test our optimized method for detection of redox metabolites from mammalian cells upon redox stress and metabolism perturbations. Redox balance was perturbed using H2O2 and diamide, metabolism was perturbed by methotrexate or oligomycin.
Application of the redox metabolite detection method for profiling redox state following pharmacologic perturbations of redox balance in cells (part II)
STUDY_SUMMARY
This study aimed to test our optimized method for detection of redox metabolites from mammalian cells upon redox stress and metabolism perturbations. Redox balance was perturbed using H2O2 and diamide, metabolism was perturbed by methotrexate or oligomycin. This experiment is an independent repeat.
INSTITUTE
Boston Children's Hospital, Harvard Medical School
Application of the redox metabolite detection method for profiling redox state following pharmacologic perturbations of redox balance in cells (part III)
STUDY_SUMMARY
This study aimed to test our optimized method for detection of redox metabolites from mammalian cells upon redox stress and metabolism perturbations. Redox balance was perturbed using H2O2 and diamide, metabolism was perturbed by methotrexate or oligomycin. This experiment is an independent repeat.
INSTITUTE
Boston Children's Hospital, Harvard Medical School
Optimization of redox metabolite detection in mammalian cells (part II)
STUDY_SUMMARY
Conditions were tested to optimize number of cells and extraction buffer for the detection of redox reactive metabolites from mammalian cells. Four different extraction buffers were compared. Derivatization of glutathion was explored as a condition as well.
INSTITUTE
Boston Children's Hospital, Harvard Medical School
Application of the redox metabolite detection method for mouse biofluids (part II)
STUDY_SUMMARY
This study was aimed at optimizing redox metabolites detection from mammalian biofluids. Three different extraction conditions were compared, including derivatization of glutathione. This study was with mouse plasma.
INSTITUTE
Boston Children's Hospital, Harvard Medical School
Timecourse on primary human highly differentiated airway epithelial cells infected with HRV-C15
STUDY_SUMMARY
At each time point (4, 12, 24 h), ALI basolateral media was collected and incubated 1:1 in ice-cold 100% methanol for 30 minutes on ice, vortexing every 10 minutes. Basolateral media was centrifuged at 20,000 × 𝑔 for 10 minutes at 4°C, and further diluted in 50% methanol prior to mass spectrometry plate loading.
Untargeted Metabolomics analysis of A549 treated with 0.5 mM extracellular ATP and 10 ng/ml TGF-beta
STUDY_SUMMARY
Control, 0.5 mM extracellular ATP and 10 ng/ml TGF-beta were used to treated 5 million A549 lung cancer cells in vitro for 2, 6 and 12 hours. The untargeted metabolomics analysis was performed on the cell lysates. The main objective of the study was to determine changes in metabolite abundances in lung cancer after treatment with extracellular ATP and TGF-beta (a known EMT inducer).
INSTITUTE
Ohio University
DEPARTMENT
Biological Sciences
LABORATORY
Dr. Xiaozhuo Chen, Edison biotechnology Institute
LAST_NAME
Shriwas
FIRST_NAME
Pratik
ADDRESS
Room 425, Parks Hall, College of Pharmacy, Ohio State University, Columbus Ohio. 43210
EMAIL
ps774614@ohio.edu
NUM_GROUPS
7
STUDY_TYPE
Untargeted metabolomics analysis in lung cancer cells
β-Adrenergic regulation of metabolism in macrophages (part-IV)
STUDY_SUMMARY
Macrophages have important roles in the immune system including clearing pathogens and wound healing. Metabolic phenotypes have been associated with functional phenotypes, where pro-inflammatory macrophages have an increased rate of glycolysis and anti-inflammatory macrophages primarily use oxidative phosphorylation. β-adrenoceptor (βAR) signalling in macrophages has been implicated in disease states such as cancer, atherosclerosis and rheumatoid arthritis. The impact of β-adrenoceptor signalling on macrophage metabolism has not been defined. Here we expand on defining the phenotype of macrophages treated with isoprenaline and describe the impact that βAR signalling has on the metabolome and proteome. We found that βAR signalling alters proteins involved in cytoskeletal rearrangement and redox control of the cell. We showed that βAR signalling in macrophages shifts glucose metabolism from glycolysis towards the tricarboxylic acid cycle and pentose phosphate pathways. We also show that βAR signalling perturbs purine metabolism by accumulating adenylate pools. Taken together these results indicate that βAR signalling shifts metabolism to support redox perturbations and upregulate proteins involved in cytoskeletal changes that may impact migration and phagocytosis processes.
INSTITUTE
Monash University
LAST_NAME
Peterson
FIRST_NAME
Amanda
ADDRESS
Drug delivery, disposition and dynamics, Pharmacy and Pharmaceutical Sciences, 381 Royal Parade, Parkville, Victoria, 3052, Australia
Impact of high intensity and moderate exercise on genomic and metabolic remodeling with age in male mice
STUDY_SUMMARY
How skeletal muscle adapts to different types of exercise intensity with age is not known. Young and old C57BL/6 male mice were assigned to either a sedentary or two types of exercise regimes consisting of daily high-intensity intermittent (HIIT) or moderate intensity continuous (MICT) training for 4 weeks, compatible with the older group’s exercise capacity. Body composition, fasting blood glucose levels, and muscle strength were improved in exercised old mice compared to sedentary controls, while the exercise benefits were absent in younger animals. Skeletal muscle exhibited structural and functional adaptations in response to exercise, as revealed by electron microscopy, OXPHOS assays, respirometry, and PGC-1 and LC3-II protein levels. Transcriptomics analysis of gastrocnemius muscle combined with liver and serum metabolomics unveiled an age-dependent metabolic remodeling provoked by exercise through mitochondrial biogenesis, energy metabolism, and cellular plasticity. These results are supportive of a tailored exercise prescription approach with the goal of improving health and ameliorating age-associated loss of muscle mass, strength and function in the elderly.
INSTITUTE
National Institutes of Health
DEPARTMENT
Experimental Gerontology Section and Translational Gerontology Branch, NIA
LAST_NAME
de Cabo
FIRST_NAME
Rafael
ADDRESS
251 Bayview Blvd. Suite 100/Room 5C214. Baltimore, MD 21224
The Metabolic Benefits of Short Cycles of Very Low Caloric Intake are Dependent on Diet Composition in Middle-Aged Mice
STUDY_SUMMARY
Diet composition, calories, and fasting times contribute to maintenance of health. Here, middle-aged mice were maintained for 5 months on 4:10 feeding cycles, consisting of 4 days of very low-calorie intake (VLCI) achieved with either standard laboratory chow (SD) or a fasting mimicking diet (FMD), followed by 10 days of ad libitum access to SD. Fat and lean mass loss was accompanied with improved performance, glucoregulation, and metabolic flexibility independent of diet composition. However, only the 4:10/SD cycles elicited a long-lasting metabolomic reprograming in serum and liver that was preserved six days after refeeding. Challenged with an obesogenic diet, cycles of VLCI achieved with either high-fat diet (HFD) or FMD during the low-calorie period did not prevent diet-induced obesity nor did they elicited a long-lasting metabolic memory, despite achieving modest metabolic flexibility. Our results highlight the importance of diet composition in mediating the metabolic benefits of short cycles of VLCI.
INSTITUTE
National Institutes of Health
DEPARTMENT
Experimental Gerontology Section and Translational Gerontology Branch, NIA
LAST_NAME
de Cabo
FIRST_NAME
Rafael
ADDRESS
251 Bayview Blvd. Suite 100/Room 5C214. Baltimore, MD 21224
Evidence that class I glutamine amidotransferase, GAT1_2.1, acts as a glutaminase in roots of Arabidopsis thaliana
STUDY_TYPE
Targeted Metabolite Quantification
STUDY_SUMMARY
In this study, we use a targeted metabolite quantification approach to demonstrate the difference in quantities of pathway intermediates between wild type Arabidopsis roots and gat1_2.1 mutants using glutamine as organic nitrogen treatment and KNO3 and Glu treatments as negative and positive controls, respectively.
Associations between the gut microbiome and metabolome in early life
STUDY_SUMMARY
The infant intestinal microbiome plays an important role in metabolism and immune development with impacts on lifelong health. The linkage between the taxonomic composition of the microbiome and its metabolic phenotype is undefined and complicated by redundancies in the taxon-function relationship within microbial communities. To inform a more mechanistic understanding of the relationship between the microbiome and health, we performed an integrative statistical and machine learning-based analysis of microbe taxonomic structure and metabolic function (using untargeted (binned) NMR and relative concentration data) in order to characterize the taxa-function relationship in early life.
INSTITUTE
University of North Carolina at Chapel Hill
DEPARTMENT
Nutrition
LABORATORY
Metabolomics and Exposome Laboratory at UNC CH Nutrition Research Institute
LAST_NAME
Sumner
FIRST_NAME
Susan
ADDRESS
500 Laureate Way, Kannapolis, NC, 28081, USA
EMAIL
susan_sumner@unc.edu
TOTAL_SUBJECTS
440
STUDY_TYPE
Untargeted and semi-targeted metabolomics analysis
Searching for prognostic biomarkers of Parkinson´s Disease development in the Spanish EPIC cohort through a multiplatform metabolomics approach
STUDY_SUMMARY
The lack of knowledge about the onset and progression of Parkinson’s disease (PD) hampers its early diagnosis and treatment. We used a multiplatform untargeted metabolomics-based approach to uncover the biochemical remodeling induced by PD in a really early and pre-symptomatic stage and unveiling early potential diagnostic biomarkers. Baseline pre-clinical plasma samples (Pre-PD n=39; control group n=39) were obtained from the European Prospective Study on Nutrition and Cancer (EPIC) cohort, which healthy volunteers were followed for around 15 years to ascertain incident PD. Our finding revealed alterations in fatty acids metabolism, mitochondrial dysfunction, oxidative stress, and gut-brain axis dysregulation. This study is of inestimable value since this is the first study conducted with samples collected many years before the disease development.
INSTITUTE
Universidad CEU San Pablo
LAST_NAME
Gonzalez-Riano
FIRST_NAME
Carolina
ADDRESS
km 0, Universidad CEU-San Pablo Urbanización Montepríncipe. M-501, 28925 Alcorcón
Metabolic Markers of Methotrexate Response in Juvenile Idiopathic Arthritis
STUDY_TYPE
Clinical
STUDY_SUMMARY
Plasma from children with juvenile idiopathic arthritis collected pre-treatment and following 3 months of treatment with methotrexate were submitted for metabolomic profiling to the NIH West Coast Metabolomics Center.
Analysis and annotation of oxidized PCs generated in vitro.
STUDY_SUMMARY
Oxidized PC16:0/PUFA (18:2, 20:4 and 22:6) generated in vitro were analyzed by LC/HRMS/MS analysis.All mass spectrometry raw data obtained in this study were deposited.
Exhaustive analysis of endogenous oxPCs in APAP-treated mice.
STUDY_SUMMARY
A single dose of APAP at 300 mg/kg body weight was intraperitoneally administered into eight-week-old C57BL/6J male mice. After extraction of hepatic lipids, oxPCs were analyzed by LC/HRMS/MS. All mass spectrometry raw data obtained in this study were deposited.
INSTITUTE
Kyushu university
LAST_NAME
Matsuoka
FIRST_NAME
Yuta
ADDRESS
3-1-1 Maidashi Higashi-ku, Fukuoka, Not USCanada, 812-8582, Japan
A metabolomics comparison of plant-based meat and grass-fed meat indicates large nutritional differences despite comparable nutrition facts labels
STUDY_SUMMARY
A new generation of plant-based meat alternatives—formulated to mimic the taste and nutritional composition of red meat—have attracted considerable consumer interest, research attention, and media coverage. This has raised questions of whether plant-based meat alternatives represent proper nutritional replacements to animal meat. Given that food sources have considerable complexity and contain a wide variety of nutrients (e.g., phenols, anti-oxidants, peptides, amino acids, fatty acids, and other carboxylic acids), the majority of which do not appear on nutrition labels, it is important to explore expanded nutrient profiles when determining whether beef and plant-based meat alternatives are nutritionally interchangeable. Important nutritional differences may exist between beef and novel plant-based alternatives, given their materials origin; however, this has not been thoroughly assessed. Given the scientific and commercial interest in plant-based meat alternatives, the goal of our study was to use untargeted metabolomics to provide an in-depth comparison of the metabolite profiles of grass-fed ground beef and a popular plant-based meat alternative.
Metabolite profiling of Malaysian Gracilaria edulis reveals Eplerenone as novel antibacterial compound for drug repurposing against MDR Bacteria
STUDY_SUMMARY
The current study re-defines a method to reveal bioactive compounds from the crude extracts of Malaysian red seaweed Gracilaria edulis, having promising antibacterial activities against selected bacterial species. Three species of Gram-positive and - negative characters were remarkably inhibited by the sequential and direct extracts of ethyl acetate and acetone. These were further separated through chromatographic methods to reveal a plethora of chemical constituents to be considered for a downstream virtual screening against selected crucial proteins of the six bacteria.
INSTITUTE
Sunway University
DEPARTMENT
Biological Sciences, Sunway University, Selangor, Malaysia
LABORATORY
Disease Complexity
LAST_NAME
Lahiri
FIRST_NAME
Chandrajit
ADDRESS
Sunway University, No. 5, Jalan Universiti, Bandar Sunway, Petaling Jaya 47500, Selangor, Malaysia
Standardized gnotobiotic mouse model for NMR based phenotyping
STUDY_SUMMARY
Germ-free mice were inoculated with 15 representative bacterial strains selected from specific pathogen-free mice. All three microbiota mouse models were generated in two different facility sites and collected plasma sample phenotyped by NMR. 58 mice from Facility 1 (32 males and 26 females) and 59 mice from Facility 2 (29 males and 30 females) were used for analysis.
Longitudinal Metabolomics of Human Plasma Reveals Robust Prognostic Markers of COVID-19 Disease Severity (part I)
STUDY_SUMMARY
There is an urgent need to identify which COVID-19 patients will develop life-threatening illness so that medical resources can be optimally allocated and rapid treatment can be administered early in the disease course, when clinical management is most effective. To aid in the prognostic classification of disease severity, we perform untargeted metabolomics on plasma from 339 patients, with samples collected at six longitudinal time points. Using the temporal metabolic profiles and machine learning, we build a predictive model of disease severity. We discover that a panel of metabolites measured at the time of study entry successfully determine disease severity. Through analysis of longitudinal samples, we confirm that the majority of these markers are directly related to disease progression and that their levels are restored to baseline upon disease recovery. Finally, we validate that these metabolites are also altered in a hamster model of COVID-19. Our results indicate that metabolic changes associated with COVID-19 severity can be effectively used to stratify patients and inform resource allocation during the pandemic.
INSTITUTE
Washington University, St. Louis
DEPARTMENT
Chemistry
LABORATORY
Patti
LAST_NAME
Patti
FIRST_NAME
Gary
ADDRESS
McMillen Chemistry Laboratory Washington University 1 Brookings Dr @ Throop Drive Rm 102 St. Louis, MO 63130-4899
Unbiased LC-MS-based metabolomics analysis for both whole cell and mitochondria metabolites to gain an insight into the role of Tug1/PGC1 axis on metabolite profiles in podocytes
STUDY_SUMMARY
unbiased LC-MS-based metabolomics analysis for both whole cell and mitochondria metabolites to gain an insight into the role of Tug1/PGC1 axis on metabolite profiles in podocytes
Quantitative analysis of bile acids in fecal samples from centenarians, elderly and young subjects.
STUDY_SUMMARY
Fecal samples from centenarians (>100 yo), elderly (85-89 yo) and young (21-55) subjects were analysed using LC-MS/MS. 48 bile acids were measured by targeted metabolomics.
Screening of unique bile acid metabolizing bacteria
STUDY_SUMMARY
We incubated individual bacterial strains at pH 7 or pH 9 with either CDCA, LCA, or 3-oxo-Δ4-LCA as starting substrates. Culture supernatants were collected after 48 hours and 14 bile acids were measured by targeted metabolomics.
Longitudinal Metabolomics of Human Plasma Reveals Robust Prognostic Markers of COVID-19 Disease Severity
STUDY_SUMMARY
There is an urgent need to identify which COVID-19 patients will develop life-threatening illness so that medical resources can be optimally allocated and rapid treatment can be administered early in the disease course, when clinical management is most effective. To aid in the prognostic classification of disease severity, we perform untargeted metabolomics on plasma from 339 patients, with samples collected at six longitudinal time points. Using the temporal metabolic profiles and machine learning, we build a predictive model of disease severity. We discover that a panel of metabolites measured at the time of study entry successfully determine disease severity. Through analysis of longitudinal samples, we confirm that the majority of these markers are directly related to disease progression and that their levels are restored to baseline upon disease recovery. Finally, we validate that these metabolites are also altered in a hamster model of COVID-19. Our results indicate that metabolic changes associated with COVID-19 severity can be effectively used to stratify patients and inform resource allocation during the pandemic.
INSTITUTE
Washington University, St. Louis
DEPARTMENT
Chemistry
LABORATORY
Patti
LAST_NAME
Patti
FIRST_NAME
Gary
ADDRESS
McMillen Chemistry Laboratory, Washington University 1 Brookings Dr @ Throop Drive, Rm 102, St. Louis, MO 63130-4899
The metabolomic resetting effect of FG4592 in AKI to CKD transition-day 21
STUDY_SUMMARY
C57BL/6 mice were anesthetized using isoflurane. UIR was induced by clamping the right renal pedicle for 45 minutes and then releasing it to allow reperfusion, leaving the left kidney intact. Sham treated mice served as controls. Each mouse was located supine on a thermostatic pad (37 °C) to maintain its body temperature throughout the whole process. After 3 days of recovery, the mice received a daily intraperitoneal (i.p.) injection of FG4592 (10 mg/kg) or vehicle for 18 consecutive days. After treatment, the mice were sacrificed. Non-target metabolomics analysis was carried out using the kidney tissues of mice sacrificed at day 21 after UIR.
Spontaneous hydrolysis and spurious metabolic properties of α-ketoglutarate esters
STUDY_SUMMARY
8988T cells treated with methyl acetate or 1 mM of alpha-ketoglutarate disodium salt or 1 mM of dimethyl-alpha-ketoglutarate for 3 hours prior to rapid quenching of metabolism and extraction of metabolites in 80% methanol (-80°C) containing internal QC standards.
INSTITUTE
University of British Columbia
LAST_NAME
Parker
FIRST_NAME
Seth
ADDRESS
950 W 28th Ave, 2099, Vancouver, British Columbia, Canada V6H 0B3
Cross-feeding between intestinal pathobionts promotes their overgrowth during undernutrition
STUDY_SUMMARY
Child undernutrition is a global health issue associated with a high burden of infectious disease. Undernourished children display an overabundance of intestinal pathogens and pathobionts, and these bacteria induce enteric dysfunction in undernourished mice; however, the cause of their overgrowth remains poorly defined. Here, we show that disease-inducing human isolates of Enterobacteriaceae and Bacteroidales spp. are capable of multi-species symbiotic cross-feeding, resulting in synergistic growth of a mixed community in vitro. Growth synergy occurs uniquely under malnourished conditions limited in protein and iron: in this context, Bacteroidales spp. liberate diet- and mucin-derived sugars and Enterobacteriaceae spp. enhance the bioavailability of iron. Analysis of human microbiota datasets reveals that Bacteroidaceae and Enterobacteriaceae are strongly correlated in undernourished children, but not in adequately nourished children, consistent with a diet-dependent growth synergy in the human gut. Together these data suggest that dietary cross-feeding fuels the overgrowth of pathobionts in undernutrition.
Prolonged cellular hypoxia leads to energetic failure and death. However, sublethal hypoxia can trigger an adaptive response called hypoxic preconditioning. While prolyl-hydroxylase (PHD) enzymes and hypoxia inducible factors (HIFs) have been identified as key elements of oxygen sensing machinery, the mechanisms by which hypoxic preconditioning protects against insults remain unclear. Here, we perform serum metabolomic profiling to assess alterations induced by hypoxic preconditioning. We discover that hypoxic preconditioning increases serum kynurenine levels and enhance kynurenine biotransformation leading to preservation of NAD+ in the post-ischemic kidney. Furthermore, we show that Indoleamine 2,3-dioxygenase 1 (Ido1) deficiency abolishes the systemic increase of kynurenine and the subsequent renoprotection generated by hypoxic preconditioning. Importantly, exogenous administration of kynurenine restores the hypoxic preconditioning in the context of Ido1 deficiency. Collectively, our findings demonstrate a critical role of Ido1/kynurenine axis in mediating hypoxic preconditioning
INSTITUTE
Northwestern University
DEPARTMENT
Medicine/Nephrology
LABORATORY
Kapitsinou
LAST_NAME
Kapitsinou
FIRST_NAME
Pinelopi
ADDRESS
303 East Superior Street
EMAIL
pinelopi.kapitsinou@northwestern.edu
NUM_GROUPS
2
TOTAL_SUBJECTS
16
NUM_MALES
16
STUDY_COMMENTS
N/A
PUBLICATIONS
Accepted in Cell Reports
CHEAR_STUDY
No
ANALYSIS_TYPE_DETAIL
N/A
STUDY_TYPE
Comparative metabolomic analysis of serum metabolites detected by untargeted LC/MS and GC/MS platform
Prolonged cellular hypoxia leads to energetic failure and death. However, sublethal hypoxia can trigger an adaptive response called hypoxic preconditioning. While prolyl-hydroxylase (PHD) enzymes and hypoxia inducible factors (HIFs) have been identified as key elements of oxygen sensing machinery, the mechanisms by which hypoxic preconditioning protects against insults remain unclear. Here, we perform serum metabolomic profiling to assess alterations induced by hypoxic preconditioning. We discover that hypoxic preconditioning increases serum kynurenine levels and enhance kynurenine biotransformation leading to preservation of NAD+ in the post-ischemic kidney. Furthermore, we show that Indoleamine 2,3-dioxygenase 1 (Ido1) deficiency abolishes the systemic increase of kynurenine and the subsequent renoprotection generated by hypoxic preconditioning. Importantly, exogenous administration of kynurenine restores the hypoxic preconditioning in the context of Ido1 deficiency. Collectively, our findings demonstrate a critical role of Ido1/kynurenine axis in mediating hypoxic preconditioning
INSTITUTE
Northwestern University
DEPARTMENT
Medicine/Nephrology
LABORATORY
Kapitsinou
LAST_NAME
Kapitsinou
FIRST_NAME
Pinelopi
ADDRESS
303 East Superior Street
EMAIL
pinelopi.kapitsinou@northwestern.edu
NUM_GROUPS
2
TOTAL_SUBJECTS
14
NUM_MALES
14
STUDY_COMMENTS
N/A
PUBLICATIONS
Accepted in Cell Reports
CHEAR_STUDY
No
ANALYSIS_TYPE_DETAIL
N/A
STUDY_TYPE
Comparative metabolomic analysis of serum metabolites detected by untargeted LC/MS and GC/MS platform
Sodium dichloroacetate stimulates cardiac mitochondrial metabolism and improves cardiac conduction in the ovine fetus during labor (part I)
STUDY_SUMMARY
Previous studies in our laboratory have suggested that the increase in stillbirth in pregnancies complicated by chronic maternal stress or hypercortisolemia is associated with cardiac dysfunction in late stages of labor and delivery. Transcriptomics analysis of the overly represented differentially expressed genes in the fetal heart of hypercortisolemic ewes indicated involvement of mitochondrial function. Sodium dichloroacetate (DCA) has been used to improve mitochondrial function in several disease states. We hypothesized that administration of DCA to laboring ewes would improve both cardiac mitochondrial activity and cardiac function in their fetuses. Four groups of ewes and their fetuses were studied: control, cortisol-infused (1 g/kg/d from 115 to term; CORT), DCA-treated (over 24h) or DCA+CORT-treated; oxytocin was delivered starting 48h before the DCA treatment. DCA significantly decreased cardiac lactate, alanine and glucose/glucose-6-phosphate and increased acylcarnitine/isobutyryl-carnitine. DCA increased mitochondrial activity, increasing oxidative phosphorylation (PCI, PCI+II)) per tissue weight or per unit of citrate synthase. DCA also decreased the duration of the QRS, attenuating the prolongation of the QRS observed in CORT fetuses. The effect to reduce QRS duration with DCA treatment correlated with increased glycerophosphocholine and serine and decreased phophocholine after DCA treatment. There were negative correlations of acylcarnitine/isobutyryl-carnitine to both HR and MAP. These results suggest that improvements in mitochondrial respiration with DCA produced changes in the cardiac lipid metabolism that favor improved conduction in the heart. DCA may therefore be an effective treatment of fetal cardiac metabolic disturbances in labor that can contribute to impairments of fetal cardiac conduction.
INSTITUTE
University of Georgia
DEPARTMENT
Biochemistry and Molecular Biology and Complex Carbohydrate Research Center, Department of Pharmacodynamics (University of Florida), Department of Physiology and Functional Genomics (University of Florida)
LABORATORY
Edison Lab, Keller-Wood Lab, and Wood Lab
LAST_NAME
Zhang
FIRST_NAME
Sicong
ADDRESS
315 Riverbend Road, Complex Carbohydrate Research Center
Sodium dichloroacetate stimulates cardiac mitochondrial metabolism and improves cardiac conduction in the ovine fetus during labor (part II)
STUDY_TYPE
untargeted NMR analysis-noesy
STUDY_SUMMARY
Previous studies in our laboratory have suggested that the increase in stillbirth in pregnancies complicated by chronic maternal stress or hypercortisolemia is associated with cardiac dysfunction in late stages of labor and delivery. Transcriptomics analysis of the overly represented differentially expressed genes in the fetal heart of hypercortisolemic ewes indicated involvement of mitochondrial function. Sodium dichloroacetate (DCA) has been used to improve mitochondrial function in several disease states. We hypothesized that administration of DCA to laboring ewes would improve both cardiac mitochondrial activity and cardiac function in their fetuses. Four groups of ewes and their fetuses were studied: control, cortisol-infused (1 g/kg/d from 115 to term; CORT), DCA-treated (over 24h) or DCA+CORT-treated; oxytocin was delivered starting 48h before the DCA treatment. DCA significantly decreased cardiac lactate, alanine and glucose/glucose-6-phosphate and increased acylcarnitine/isobutyryl-carnitine. DCA increased mitochondrial activity, increasing oxidative phosphorylation (PCI, PCI+II)) per tissue weight or per unit of citrate synthase. DCA also decreased the duration of the QRS, attenuating the prolongation of the QRS observed in CORT fetuses. The effect to reduce QRS duration with DCA treatment correlated with increased glycerophosphocholine and serine and decreased phophocholine after DCA treatment. There were negative correlations of acylcarnitine/isobutyryl-carnitine to both HR and MAP. These results suggest that improvements in mitochondrial respiration with DCA produced changes in the cardiac lipid metabolism that favor improved conduction in the heart. DCA may therefore be an effective treatment of fetal cardiac metabolic disturbances in labor that can contribute to impairments of fetal cardiac conduction.
INSTITUTE
University of Georgia
DEPARTMENT
Biochemistry and Molecular Biology and Complex Carbohydrate Research Center, Department of Pharmacodynamics (University of Florida), Department of Physiology and Functional Genomics (University of Florida)
LABORATORY
Edison Lab, Keller-Wood Lab, and Wood Lab
LAST_NAME
Zhang
FIRST_NAME
Sicong
ADDRESS
315 Riverbend Road, Complex Carbohydrate Research Center
Effects of GP130 Antagonism on Right Ventricular Metabolism in Monocrotaline Rats
STUDY_SUMMARY
We used global metabolomics profiling to evaluate right ventricular metabolism in control, monocrotaline rats treated with vehicle, and monocrotaline rats treated with SC144 (GP130 antagonists).
1H NMR Metabolomics to elucidate signaling pathway
STUDY_SUMMARY
Metabolomics investigation of the phytoplankton Alexandrium minutum with and without copepod cues in order to explore cell signaling involved in toxin induction.
INSTITUTE
Georgia Institute of Technology
DEPARTMENT
School of Biological Sciences, School of Chemistry and Biochemistry, Center for Microbial Dynamics and Infection, Parker H. Petit Institute for Bioengineering and Bioscience
LABORATORY
Kubanek Lab
LAST_NAME
Brown
FIRST_NAME
Emily
ADDRESS
950 Atlantic Dr Atlanta, Georgia USA 30332
EMAIL
julia.kubanek@biosci.gatech.edu
PHONE
404-894-8424
NUM_GROUPS
2
TOTAL_SUBJECTS
40
STUDY_COMMENTS
Part 1 of 3. This part includes NMR analysis of polar metabolites using oPLSDA. Parts 2 and 3 inlcude NMR analysis of nonpolar metabolites and the corresponding mass spectrometry metabolomics for both polar and non-polar metabolites.
1H NMR Metabolomics to elucidate signaling pathway
STUDY_SUMMARY
Metabolomics investigation of the phytoplankton Alexandrium minutum with and without copepod cues in order to explore cell signaling involved in toxin induction.
INSTITUTE
Georgia Institute of Technology
DEPARTMENT
School of Biological Sciences, School of Chemistry and Biochemistry, Center for Microbial Dynamics and Infection, Parker H. Petit Institute for Bioengineering and Bioscience
LABORATORY
Kubanek Lab
LAST_NAME
Brown
FIRST_NAME
Emily
ADDRESS
950 Atlantic Dr Atlanta, Georgia USA 30332
EMAIL
julia.kubanek@biosci.gatech.edu
PHONE
404-894-8424
NUM_GROUPS
2
TOTAL_SUBJECTS
40
STUDY_COMMENTS
Part 2 of 3. This part includes NMR analysis of non-polar metabolites using oPLSDA. Parts 1 and 3 inlcude NMR analysis of polar metabolites and the corresponding mass spectrometry metabolomics for both polar and non-polar metabolites.
LC-MS for Predator Cues Target Signaling Pathways in Toxic Algal Metabolome Protocol
STUDY_SUMMARY
Metabolomics investigation of the phytoplankton Alexandrium minutum with and without copepod cues in order to explore cell signaling involved in toxin induction.
Involvement of Mieap in Cardiolipin metabolism (part I)
STUDY_SUMMARY
Quantitative assessment of total cardiolipin (CL) and comparison of CL species conducted with A549 (Ad-Mieap infected vs. non-infected) and LS174T cells (LS174T-cont vs. Mieap-KD). The A549 cells were harvested 24 hr after infection with Ad-Mieap and were compared with non-infected cells by mass spectrometric analysis. The LS174T-cont and Mieap-KD cells incubated under a normal condition were harvested and subjected to mass spectrometric analysis.
NMR Differentiating toxic and nontoxic congeneric harmful algae using the non-polar metabolome (Experiment 1)
STUDY_TYPE
1H NMR Metabolomics to compare toxic and non-toxic species
STUDY_SUMMARY
Metabolomics comparison of toxic and non-toxic species of phytoplankton from the genus Alexandrium.This study was carried out using 2 pairwise experiments, A. catenella compared to A. tamarense (Experiment 1) and A. pacificum compared to A. tamarense (Experiment 2). This study includes the NMR data from Experiment 1.
INSTITUTE
Georgia Institute of Technology
DEPARTMENT
School of Biological Sciences, School of Chemistry and Biochemistry, Center for Microbial Dynamics and Infection, Parker H. Petit Institute for Bioengineering and Bioscience
LABORATORY
Kubanek Lab
LAST_NAME
Brown
FIRST_NAME
Emily
ADDRESS
950 Atlantic Dr Atlanta, Georgia USA 30332
EMAIL
julia.kubanek@biosci.gatech.edu
PHONE
404-894-8424
NUM_GROUPS
2
TOTAL_SUBJECTS
30
STUDY_COMMENTS
Part 1 of 3. This part includes NMR analysis of non-polar metabolites from Experiment 1 using oPLSDA. Parts 2 and 3 inlcude NMR analysis of non-polar metabolites from Experiment 2 and the corresponding mass spectrometry metabolomics for both Experiments 1 and 2.
NMR Differentiating toxic and nontoxic congeneric harmful algae using the non-polar metabolome (Experiment 2)
STUDY_TYPE
1H NMR Metabolomics to compare toxic and non-toxic species
STUDY_SUMMARY
Metabolomics comparison of toxic and non-toxic species of phytoplankton from the genus Alexandrium.This study was carried out using 2 pairwise experiments, A. catenella compared to A. tamarense (Experiment 1) and A. pacificum compared to A. tamarense (Experiment 2). This study includes the NMR data from Experiment 2.
INSTITUTE
Georgia Institute of Technology
DEPARTMENT
School of Biological Sciences, School of Chemistry and Biochemistry, Center for Microbial Dynamics and Infection, Parker H. Petit Institute for Bioengineering and Bioscience
LABORATORY
Kubanek Lab
LAST_NAME
Brown
FIRST_NAME
Emily
ADDRESS
950 Atlantic Dr Atlanta, Georgia USA 30332
EMAIL
julia.kubanek@biosci.gatech.edu
PHONE
404-894-8424
NUM_GROUPS
2
TOTAL_SUBJECTS
30
STUDY_COMMENTS
Part 2 of 3. This part includes NMR analysis of non-polar metabolites from Experiment 2 using oPLSDA. Parts 1 and 3 inlcude NMR analysis of non-polar metabolites from Experiment 1 and the corresponding mass spectrometry metabolomics for both Experiments 1 and 2.
Mitochondrial-Derived Compartments Facilitate Cellular Adaptation to Amino Acid Stress
STUDY_SUMMARY
Amino acids are essential building blocks of life. However, increasing evidence suggests that elevated amino acids cause cellular toxicity associated with numerous metabolic disorders. How cells cope with elevated amino acids remains poorly understood. Here, we show that a previously identified cellular structure, the mitochondrial-derived compartment (MDC), functions to protect cells from amino acid stress. In response to amino acid elevation, MDCs are generated from mitochondria, where they selectively sequester and deplete SLC25A nutrient carriers and their associated import receptor Tom70 from the organelle. Generation of MDCs promotes amino acid catabolism, and their formation occurs simultaneously with transporter removal at the plasma membrane via the multi-vesicular body (MVB) pathway. Combined loss of vacuolar amino acid storage, MVBs and MDCs renders cells sensitive to high amino acid stress. Thus, we propose that MDCs operate as part of a coordinated cell network that facilitates amino acid homoeostasis through post-translational nutrient transporter remodeling.
INSTITUTE
University of Utah School of Medicine
DEPARTMENT
Biochemistry
LABORATORY
Hughes Lab
LAST_NAME
Hughes
FIRST_NAME
Adam
ADDRESS
15 N Medical Drive East, RM 4100, Salt Lake City, UT, 84112, USA
Urine-Based Metabolomics and Machine Learning Reveals Metabolites Associated with Renal Cell Carcinoma Progression NMR (part-I)
STUDY_SUMMARY
Every year, hundreds of thousands of cases of renal carcinoma (RCC) are reported worldwide. Accurate staging of the disease is important for treatment and prognosis purposes; however, contemporary methods such as computerized tomography (CT) and biopsies are expensive and prone to sampling errors, respectively. As such, a non-invasive diagnostic assay for staging would be beneficial. This study aims to investigate urine metabolites as potential biomarkers to stage RCC. In the study, we identified a panel of such urine metabolites with machine learning techniques.
Pseudoexfoliation aqueous humor lipidome suggests enrichment of specific pathways
STUDY_SUMMARY
Pseudoexfoliation syndrome (PEX) is systemic disorder that manifests as white, fluffy, proteinaceous fibrillar material throughout the body. In the eye such deposits result in Pseudoexfoliation glaucoma (PEXG), due to impeding aqueous humor outflow. Serum lipid alterations and increased lipid peroxidation have been reported in PEX. We report first ever comprehensive lipid profiling of the aqueous humor (AH) of PEXG. Our untargeted lipidomic analysis of 23 non-glaucomatous control, 19 primary open angle glaucoma, 9 PEX, and 14 PEXG AH with 13 deuterated lipid internal standards for normalization among the lipid classes resulted in the combined identification of 489 lipid species within 26 lipid classes across PEX, PEXG, POAG, and control AH. The mean total lipid content in the AH across samples showed that control AH (mean peak area 13.54 ± 56.1) had, on average, greater total lipid content than PEX (4.21 ± 10.90), PEXG (9.08 ± 25.97), and POAG (5.66 ± 15.75) samples. Multiple cholesterol esters (ChE), phosphatidylcholines (PC), triglycerides (TG), and ceramides (Cer) were present in higher concentrations for the PEXG AH samples. Some of the lipids found in high concentrations in the PEXG samples are ChE(16:0), ChE(20:3), ChE(18:1), ChE(18:3), ChE(22:6), ChE(18:2), ChE(20:4), PC(16:0/16:0), PC(16:0/18:2), TG(18:1/18:1/20:4), and Cer(t18:0/24:0). The CerG2GNAc1(d34:1) was enriched in control samples and depleted both in PEX and PEXG samples. The PC (18:0/18:2), PC (36:2), and PC (34:1e) are in low concentrations for PEX but highly concentrated in PEXG, despite both having similar material deposits, suggesting they are fundamentally different in composition. Elevations in Apolipoprotein A-I (APOA1) correlated to increase abundance of PC lipid species in the AH of patients with PEXG. Machine learning prediction with three supervised logistic regression binary classification tasks showed 1) POAG vs control, with 86% accuracy 2) PEXG vs control, with 71% accuracy and 3) PEX vs control, with 86% accuracy, respectively.
Metabolomics characterized concentration-dependent metabolic influence of magnesium on biofilm formation in Escherichia coli (Part 2)
STUDY_SUMMARY
Biofilms are broadly formed by a diversity of microorganisms that enable them to adapt stressful environments. Biofilms often impose harmful influences in many niches, as they can cause food contamination, antibiotics resistance, and environmental issues. However, eradicating biofilms remains difficult since the formation mechanism of biofilms are still incompletely clarified. In this study, we aimed at exploring the regulatory role of magnesium (Mg2+) on biofilm formation in Escherichia coli (E. coli) using phenotype visualization combined with targeted metabolomics method. We found that Mg2+ could exert significant influence on biofilm formation in a concentration-dependent manner by regulating phenotypic morphology and triggering metabolic modifications of biofilm. Phenotypic imaging revealed that increasing concentration of Mg2+ gradually inhibited biofilm formation, Mg2+ was observed to restore the microstructure of E. coli strain in biofilms to that in the relevant planktonic cells. In addition, our metabolomics analysis characterized 20 differential metabolites and associated 2 metabolic pathways including nucleotide metabolism and amino acid metabolism that were notably modified during biofilm formation under the treatments of different concentrations of Mg2+. Altogether, our work provides a novel insight into the influence of Mg2+ on biofilm formation at a metabolic level, which are implicated in the novel solution to disturb biofilm formation through the regulation of Mg2+ and functional metabolite interaction, then biofilms associated harmful impacts in different niches could be well tangled accordingly.
INSTITUTE
Shanghai Center for Systems Biomedicine, Shanghai Jiaotong University
DEPARTMENT
Shanghai Center for Systems Biomedicine
LABORATORY
Lu Group
LAST_NAME
Lu
FIRST_NAME
Haitao
ADDRESS
800 Dongchuan RD. Minhang District, Shanghai, Shanghai, 200240, China
Urinary signature of chronic kidney disease in patients with severe obesity by CE-MS
STUDY_TYPE
Human nephropathy in CKD obese patients
STUDY_SUMMARY
Urine metabolomic characterization of severe obese patients with and without chronic kidney disease (CKD) by CE-MS. Analysis was performed in patients before and after bariatric surgery. In the present studio, samples obtained from CKD patients with severe obesity before bariatric surgery will be referred as OD (obese disease). Samples obtained from CKD patients with severe obesity after bariatric surgery will be referred as ODBS (Obese disease bariatric surgery). Patients with severe obesity without CKD will be referenced as O (obese) and after BS, OBS (obese bariatric surgery). In healthy group, when results refer to the first void urine samples, the acronym will be Healthy1V, and the acronym for urine samples collected at 24-hour will be Healthy24h.
Phytoplankton-derived metabolites fuel a large fraction of heterotrophic bacterial production in the global ocean, yet methodological challenges have limited our knowledge of organic molecules transferred between these two microbial groups. In an experimental bloom study in which the diatom Thalassiosira pseudonana was co-cultured with three heterotrophic marine bacteria, we concurrently measured diatom endometabolites (i.e., potential exometabolite supply) by nuclear magnetic resonance (NMR) spectroscopy and bacterial gene expression (i.e., potential exometabolite uptake) by metatranscriptomic sequencing.
INSTITUTE
University of Georgia
DEPARTMENT
Department of Marine Sciences; Complex Carbohydrate Research Center
The largest living rodent dwelling Pantanal wetlands and Amazon basin, capybara, can efficiently depolymerize and utilize lignocellulosic biomass through microbial symbiotic mechanisms yet elusive. Herein, combining multi-meta-omics approaches, carbohydrate enzymology and X-ray crystallography, we elucidated the microbial community composition and structure, enzymatic systems and metabolic pathways involved in the conversion of recalcitrant dietary fibers into short-chain fatty acids, a main energy source for the host. The high efficiency of this microbiota in the deconstruction of plant polysaccharides is underpinned on the combination of unique enzymatic mechanisms from Fibrobacteres to degrade cellulose with a broad arsenal of Carbohydrate-Active enZymes (CAZymes) organized in polysaccharide utilization loci (PULs) from Bacteroidetes, to tackle with complex hemicelluloses typically found in gramineous and aquatic plants. Exploring the genomic dark matter of this community, two novel CAZy families were unveiled including a glycoside hydrolase family of β-galactosidases and a carbohydrate-binding module family involved in xylan binding that establishes an unprecedented three-dimensional fold among associated modules to CAZymes. Together, these results demonstrate at community and molecular levels how the capybara gut microbiota orchestrates the deconstruction and utilization of dietary fibers, representing an untapped reservoir of new and intricate enzymatic mechanisms to overcome the lignocellulose recalcitrance, a central challenge toward a bio-based and sustainable economy.
INSTITUTE
Brazilian Center for Research in Energy and Materials (CNPEM)
LAST_NAME
Persinoti
FIRST_NAME
Gabriela
ADDRESS
Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas, Sao Paulo, 13083-100, Brazil
Metabolites Associated with Gestational Diabetes in Plasma
STUDY_TYPE
Case:Control ancillary analysis of RCT
STUDY_SUMMARY
"Gestational diabetes mellitus (GDM) significantly increases maternal and fetal health risks, but factors predictive of GDM are poorly understood. Plasma metabolomics analyses were conducted in early pregnancy to identify potential biomarkers for early prediction of Gestational Diabetes Mellitus (GDM). Sixty-eight pregnant women with overweight/obesity from a clinical trial of a lifestyle intervention were included. Participants who developed GDM (n=34; GDM group) were matched on treatment group, age, body mass index, and ethnicity with those who did not develop GDM (n=34; Non-GDM group). Blood draws were completed early in pregnancy (10-16 weeks). Plasma samples were analyzed by UPLC-MS using three metabolomics assays. "
INSTITUTE
California Polytechnic State University
DEPARTMENT
Food Science and Nutrition
LABORATORY
Cal Poly Metabolomics Service Center
LAST_NAME
La Frano
FIRST_NAME
Michael
ADDRESS
CALIFORNIA POLYTECHNIC STATE UNIVERSITY, 1 GRAND AVE
Identifying metabolite changes in human islets treated with Phospho-BAD mimicry and Inflammatory cytokines
STUDY_SUMMARY
The goal of this study was to associate metabolite changes with protection of human islets from cell death induced by the diabetogenic stress of inflammatory cytokines. Protection of human islet viability was accomplished via enhanced glucose metabolism using phospho-BAD mimicry peptide treatment.
Metabonomics analysis reveals the physiological mechanism of promoting maize shoots growth under negative pressure to stabilize soil water content
STUDY_SUMMARY
The purpose of this study is to analyze maize shoots growth under negative pressure to stabilize soil water content，Maize plants were subjected to two irrigation treatments. The first treatment was soil moisture dry-wet cycles, which was obtained using drip irrigation (control, DW). The second treatment was negative pressure to stabilize soil water content treatment (SW), which was obtained using the negative pressure irrigation (NPI) system.
INSTITUTE
Heilongjiang Bayi Agricultural University
LAST_NAME
Zhang
FIRST_NAME
Jili
ADDRESS
High tech Zone, Longfei District, Daqing, Heilongjiang, 163319, China
Timecourse exometabolome analysis of glucose grown Rubrivivax benzoatilyticus cells
STUDY_TYPE
Timecourse experiment
STUDY_SUMMARY
Bacterial cells were grown on glucose under photoheterotrophic conditions for 18 days. Spent media of cells, harvested at 3rd, 9th and 18th day of growth, was vacuum dried and the metabolome was extracted in methanol. The extracted metabolites were derivatized and analyzed using GC-MS.
Data on changes in lipid profiles during differentiation and maturation of human subcutaneous white adipocytes analyzed using chromatographic and bioinformatics tools
STUDY_SUMMARY
Three cell lines of Caucasian-derived subcutaneous preadipocytes were divided into five stages (stage-1 to stage-5) from subcutaneous preadipocytes to mature subcutaneous adipocytes filled with many lipid droplets. Lipids were extracted from cells in each stage and processed using untargeted liquid chromatography and Q-Exactive Orbitrap tandem mass spectrometry. The lipids were identified using LipidSearch 4.2.13.
INSTITUTE
Hamamatsu University School of Medicine
LAST_NAME
Kitamoto
FIRST_NAME
Takuya
ADDRESS
1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan
Analytical methodology for a metabolome atlas of goat’s plas-ma, milk and feces using 1H-NMR and UHPLC-HRMS
STUDY_SUMMARY
Metabolomics has been increasingly used in animal and food sciences. Animal health is one of the most important factor that can also alter animal integrity and welfare. Some studies have al-ready investigated the link between health and metabolic profile of dairy animals. These studies in metabolomics often consider a single type of sample using a single analytical platform (Nu-clear Magnetic Resonance or Mass Spectrometry). Only few studies with multi-platform ap-proaches are also used with a single or a multi type of sample, but they mainly consider dairy cows metabolome although dairy goats present similar diseases, that it could be interesting to detect early to preserve animal health and milk production. This study aims to create a metabol-ic atlas of goat plasma, milk and feces, based on healthy animals. Our study describes a Standard Operating Procedure for three goat matrices: blood plasma, milk, and feces using multiple plat-forms (NMR (1H), UHPLC (RP)-MS and UHPLC (HILIC)-MS) that follows a unique sample prep-aration procedure for each sample type to be analyzed on multi-platforms basis. Our method was evaluated for its robustness and allowed a better characterization of goat metabolic profile in healthy conditions.
INSTITUTE
INSERM
LAST_NAME
Martias
FIRST_NAME
Cecile
ADDRESS
10 Boulevard tonnelé, Tours, Indre et Loire, 37000, France
Analytical methodology for a metabolome atlas of goat’s plasma, milk and feces using 1H-NMR and UHPLC-HRMS:MS/milk
STUDY_SUMMARY
Metabolomics has been increasingly used in animal and food sciences. Animal health is one of the most important factors that can also alter animal integrity and welfare. Some studies have already investigated the link between health and metabolic profile of dairy animals. These studies in metabolomics often consider a single type of sample using a single analytical platform (Nuclear Magnetic Resonance or Mass Spectrometry). Only few studies with multi-platform approaches are also used with a single or a multi type of sample, but they mainly consider dairy cows metabolome although dairy goats present similar diseases, that it could be interesting to detect early to preserve animal health and milk production. This study aims to create a metabolic atlas of goat plasma, milk, and feces, based on healthy animals. Our study describes a Standard Operating Procedure for three goat matrices: blood plasma, milk, and feces using multiple platforms (NMR (1H), UHPLC (RP)-MS and UHPLC (HILIC)-MS) that follows a unique sample preparation procedure for each sample type to be analyzed on multi-platforms basis. Our method was evaluated for its robustness and allowed a better characterization of goat metabolic profile in healthy conditions.
INSTITUTE
INSERM
LAST_NAME
Martias
FIRST_NAME
Cecile
ADDRESS
10 Boulevard tonnelé, Tours, Indre et Loire, 37000, France
Anti-oxidative metabolism measurement in mammalian cells and tissues by quantitative LC/MS method (I)
STUDY_SUMMARY
Anti-oxidative metabolism measurement in mammalian cells and tissues by quantitative LC/MS method to establish baseline metabolism in mouse controls 0-48hrs in CSF and hippocampus.
INSTITUTE
Boston Children's Hospital, Harvard Medical School
Anti-oxidative metabolism measurement in mammalian cells and tissues by quantitative LC/MS method (II)
STUDY_SUMMARY
Anti-oxidation metabolism measurement in mouse CSF by quantitative LC/MS method to establish MTX effects on mouse metabolism in mouse controls 0-48hrs in CSF (repeat of 20200124 ChP-MTX-Anti-oxidative-study-test)
INSTITUTE
Boston Children's Hospital, Harvard Medical School
Anti-oxidation metabolism measurement in mammalian cells and tissues by quantitative LC/MS method (III)
STUDY_SUMMARY
Anti-oxidative metabolism measurement in mouse CSF by quantitative LC/MS method of mouse CSF at 24H of MTX treatment, for either control GFP or SOD3-overexpressing ChP mice.
INSTITUTE
Boston Children's Hospital, Harvard Medical School
Metabolomic Fingerprinting of Human High Grade Serous Ovarian Carcinoma Cell Lines
STUDY_SUMMARY
Focusing on defining the metabolomic basis of intratumoral heterogeneity in ovarian cancer, the metabolic diversity of a panel of high grade serous ovarian carcinoma (HGSOC) cell-lines we investigated using a metabolomics platform that interrogate 731 compounds. Metabolic fingerprinting followed by 2-dimensional and 3-dimensional principal component analysis defined the heterogeneity of the HGSOC cells and clustered them into five distinct metabolic groups. An overall increase in the metabolites associated with aerobic glycolysis and phospholipid metabolism were observed in the majority of the cancer cells. A preponderant increase in the levels of metabolites involved in trans-sulfuration and glutathione synthesis was also observed. Subsets of HGSOC cells showed an increase in the levels of 5-Hydroxytryptamine, gamma-aminobutyric acid, or glutamate, pointing to their potential role as oncometabolites. In summary, our results identify increased glycolysis, phospholipid metabolism and amino acid metabolism with the resultant increase in the levels of 5-Hydoxytryptamine, GABA, and Glutamate as metabolomic correlates underlying the heterogeneity of ovarian cancer cell lines.
INSTITUTE
University of Oklahoma Health Sciences Center
DEPARTMENT
Cell Biology
LABORATORY
Danny N Dhanasekaran
LAST_NAME
Jayaraman
FIRST_NAME
Muralidharan
ADDRESS
975 NE 10th street, BRC1470, Oklahoma City, Oklahoma, 73104, USA
THEM6-mediated lipid remodelling sustains stress resistance in cancer (Part 2)
STUDY_TYPE
Lipidomics
STUDY_SUMMARY
Despite the clinical benefit of androgen-deprivation therapy (ADT), the majority of patients with advanced prostate cancer (PCa) ultimately develop lethal castration-resistant prostate cancer (CRPC). In this study, we identified thioesterase superfamily member 6 (THEM6) as a marker of ADT resistance in PCa. In patients, THEM6 expression correlates with progressive disease and is associated with poor survival. THEM6 deletion reduces in vivo tumour growth and restores castration sensitivity in orthograft models of CRPC. Mechanistically, THEM6 is located at the endoplasmic reticulum (ER) membrane and controls lipid homeostasis by regulating intracellular levels of ether lipids. As a consequence, THEM6 loss in CRPC cells significantly alters ER function, preventing lipid-mediated induction of ATF4 and reducing de novo sterol biosynthesis. Finally, we show that THEM6 is required for the establishment of the MYC-induced stress response. Thus, similar to PCa, THEM6 loss significantly impairs tumorigenesis in the MYC-dependent subtype of triple negative breast cancer. Altogether our results highlight THEM6 as a novel component of the treatment-induced stress response and a promising target for the treatment of CRPC and MYC-driven cancer.
THEM6-mediated lipid remodelling sustains stress resistance in cancer (Part 3)
STUDY_TYPE
Lipidomics
STUDY_SUMMARY
Despite the clinical benefit of androgen-deprivation therapy (ADT), the majority of patients with advanced prostate cancer (PCa) ultimately develop lethal castration-resistant prostate cancer (CRPC). In this study, we identified thioesterase superfamily member 6 (THEM6) as a marker of ADT resistance in PCa. In patients, THEM6 expression correlates with progressive disease and is associated with poor survival. THEM6 deletion reduces in vivo tumour growth and restores castration sensitivity in orthograft models of CRPC. Mechanistically, THEM6 is located at the endoplasmic reticulum (ER) membrane and controls lipid homeostasis by regulating intracellular levels of ether lipids. As a consequence, THEM6 loss in CRPC cells significantly alters ER function, preventing lipid-mediated induction of ATF4 and reducing de novo sterol biosynthesis. Finally, we show that THEM6 is required for the establishment of the MYC-induced stress response. Thus, similar to PCa, THEM6 loss significantly impairs tumorigenesis in the MYC-dependent subtype of triple negative breast cancer. Altogether our results highlight THEM6 as a novel component of the treatment-induced stress response and a promising target for the treatment of CRPC and MYC-driven cancer.
In order to identify metabolites descriptive of alterations of the working themperature during the process of anaerobic digestion, we performed untargeted metabolomics on samples of sewage sludge collected from two reactors working in parallel but with different temperature settings.
INSTITUTE
INRAE
LAST_NAME
Chapleur
FIRST_NAME
Olivier
ADDRESS
1 rue Pierre-Gilles de Gennes, 92761 Antony Cedex, FRANCE
Glycine betaine uptake and metabolism in marine microbial communities
STUDY_TYPE
Quantitative and qualitative exploration of isotope-labeled glycine betaine uptake and use in natural marine microbial communities
STUDY_SUMMARY
Glycine betaine (GBT) is a component of labile dissolved organic matter and a compatible solute in high concentrations in marine microbial populations. GBT has complex biochemical potential, but, once taken up from the environment, the cellular fate of the carbon and nitrogen from GBT is unknown. Here we determine the uptake kinetics and metabolism of GBT in two natural microbial communities characterized by different nitrate concentrations in the North Pacific transition zone. Dissolved GBT had maximum uptake rates of 0.36 and 0.56 nM hr -1 and half-saturation constants of 79 and 11 nM in the high nitrate and low nitrate stations, respectively. GBT taken into cells was predominantly retained as an untransformed compatible solute. A portion of GBT was transformed into other metabolites, through characterized and uncharacterized pathways. Where nitrate was scarce, GBT was primarily catabolized via the demethylation to glycine. Resulting metabolites were used to build protein biomass, and remineralized ammonia was re-assimilated into cells. Gene expression data from this region show that bacteria, especially SAR11, are the dominant organisms expressing the demethylation genes. Where nitrate concentrations were higher, more GBT was used for choline synthesis. Our data highlight undiscussed metabolic pathways and potential routes of microbial metabolite exchange.
Metabolomic Profiling of Human Pluripotent Stem Cell Differentiation into Lung Progenitors
STUDY_SUMMARY
Metabolism is vital to cellular function and tissue homeostasis during human lung development. In utero, embryonic pluripotent stem cells undergo endodermal differentiation towards a lung progenitor cell fate that can be mimicked in vitro using induced human pluripotent stem cells (hiPSCs) to study genetic mutations. To identify differences between wild type and surfactant protein B (SFTPB)-deficient cell lines during endoderm specification towards lung, we used an untargeted metabolomics approach to evaluate the developmental changes in metabolites. We found that the metabolites most enriched during the differentiation from pluripotent stem cell to lung progenitor cell, regardless of cell line, were sphingomyelins and phosphatidylcholines, two important lipid classes in fetal lung development. The SFTPB mutation had no metabolic impact on early endodermal lung development. The identified metabolite signatures during lung progenitor cell differentiation may be utilized as biomarkers for normal embryonic lung development.